Patent Publication Number: US-2023138679-A1

Title: Novel mutations that enhance the dna cleavage activity of acidaminococcus sp. cpf1

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of Ser. No. 16/536,256, filed Aug. 8, 2019, and entitled “NOVEL PROTEIN MUTANTS THAT ENHANCE THE DNA CLEAVAGE ACTIVITY OF  ACIDAMINOCOCCUS SP . CPF1,” which claims benefit of priority under 35 U.S.C. 119 to U.S. Provisional patent application Ser. No. 62/870,268, filed Jul. 3, 2019 and entitled “OPTIMIZED CAS12A (CPF1) PROTEINS FOR EFFICIENT GENOME EDITING IN EUKARYOTIC CELLS,” U.S. Provisional patent application Ser. No. 62/749,607, filed Oct. 23, 2018 and entitled “DEEP-SCANNING MUTAGENESIS UNCOVERS NOVEL MUTATIONS THAT ENHANCE THE DNA CLEAVAGE ACTIVITY OF  ACIDAMINOCOCCUS SP . CAS12A/CAS12A AT NON-CANONICAL TTTT PAM SITES” and U.S. Provisional patent application Ser. No. 62/716,138, filed Aug. 8, 2018 and entitled “NOVEL MUTATIONS THAT ENHANCE THE DNA CLEAVAGE ACTIVITY OF  ACIDAMINOCOCCUS SP . CPF1,” the contents of each application are herein incorporated by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     This invention pertains to the ability to cleave double-stranded DNA of living organisms at precise positions with the CRISPR/Cas12a (Cpf1) nuclease system. In particular, a series of recombinant Cas12a proteins are described that are useful in a eukaryotic cell context. 
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing that has been submitted in XML format via Patent Center and is hereby incorporated by reference in its entirety. The XML copy, created on Dec. 6, 2022, is named IDT01-013-US-CON.XML, and is 680,415 bytes in size. 
     BACKGROUND OF THE INVENTION 
     Cas12a is an RNA-guided endonuclease found in bacterial species including  Acidaminococcus sp . and is part of the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) adaptive immune system. Cas12a is guided to a 21˜24-nt DNA target sequence, or commonly referred as protospacer, by a target site-specific 21˜24-nt complementary RNA. The Cas12a-gRNA ribonucleoprotein (RNP) complex mediates double-stranded DNA breaks (DSBs), which are then repaired by either the non-homologous end joining (NHEJ, typically introduces mutations or indels at the cut site), or the homology directed repair (HDR) system for precise editing if a suitable template nucleic acid is present. 
     Critical to the recognition of correct DNA target for Cas12a includes both crRNA and the canonical “TTTV” protospacer adjacent motif (PAM), which is a 4-bp sequence immediately upstream of the protospacer. Compared to the 2-bp NGG PAM of Cas9 from  Streptococcus pyogenes , Cas12a expanded the targetable loci in genome editing, particularly over the AT-rich sites that are inaccessible to the Cas9 system. However, due to its relatively low enzymatic activity, the likelihood that efficient genome editing can be achieved for a given site is much lower than that of the Cas9 system, which restricts its broader application. As the consequence, the Cas12a system is frequently considered as an alternative approach only when the genomic site is not targetable by Cas9. 
     Protein engineering by mutagenesis can alter the preference of PAM sequence of CRISPR system. Through a structural-guided mutagenic screening of residues in proximity of PAM sequence, previous study has identified two AsCpf1 variants that are compatible with TYCV and TATV PAMs, respectively. Although these variants collectively expanded the targetable sites of Cpf1 system over the coding region of the human genome by 3-fold, the utility of each individual variant is still limited, due to their mutually exclusive requirement of PAM sequences (TYCV vs TATV vs TTTV). Identifying Cpf1 variants with shorter PAM and greater sequence flexibility without sacrificing the activity at canonical PAM sites is highly desirable. 
     Thus, there is a need to enhance the utility of Cas12a. One aspect of the present application is to enhance the utility of Cpf1 by broadening its PAM compatibility. In this regard, certain novel AsCas12a variants with enhanced activity have been discovered. Another desired objective is to maximize delivery of the bacterial protein to the eukaryotic nucleus while simultaneously avoiding disruption of basic Cas12a function. Since the Cas12a is a bacterial protein, certain molecular genetic obstacles must first be overcome before one can achieve successful delivery of the protein to eukaryotic cells. This invention provides unique solutions to achieving these objectives. 
     BRIEF SUMMARY OF THE INVENTION 
     In a first aspect, A CRISPR-associated protein comprising a polypeptide encoding a variant of AsCpf1 is provided. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). 
     In a second aspect, a CRISPR ribonucleoprotein complex is provided. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein including a polypeptide encoding a variant of AsCpf1. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). 
     In a third aspect, a method of increasing efficiency of gene editing at TTTN PAM sites in a cell with a CRISPR ribonucleoprotein complex is provided. The method includes the step of contacting a cell with the CRISPR ribonucleoprotein complex. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein including a polypeptide encoding a variant of AsCpf1. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). 
     In a fourth aspect, a kit comprising a guide RNA and a CRISPR-associated protein is provided. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCpf1. 
     In a fifth aspect, CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. 
     In a sixth aspect, a CRISPR ribonucleoprotein complex is provided. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. 
     In a seventh aspect, a method of increasing efficiency of gene editing at non-canonical TTTT PAM sites in a cell with a CRISPR ribonucleoprotein complex is provided. The method includes a step of contacting a cell with the CRISPR ribonucleoprotein complex that includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. 
     In an eighth aspect, a kit including a guide RNA and a CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a is provided. The variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. 
     In a ninth aspect, a nucleic acid encoding a CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a is provided. The variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. 
     In a tenth aspect, a polynucleotide sequence encoding a Cas12a polypeptide is provided. The polynucleotide sequence includes one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In an eleventh aspect, an amino acid sequence encoding a Cas12a polypeptide is provided. The amino acid sequence includes one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a twelfth aspect, a CAS endonuclease system comprising an expression cassette encoding a polynucleotide sequence encoding a Cas12a polypeptide is provided. The includes one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In a thirteenth aspect, CAS endonuclease system comprising an amino acid sequence encoding a Cas12a polypeptide is provided The amino acid sequence includes one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a fourteenth aspect, a method of performing genome editing in a eukaryotic cells is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising an expression cassette encoding a polynucleotide sequence encoding a Cas12a polypeptide, comprising one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In a fifteenth aspect, a method of performing genome editing in a eukaryotic cell is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising an amino acid sequence encoding a Cas12a polypeptide comprising one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a sixteenth aspect, an CRISPR-associated protein comprising a fusion polypeptide is provided. The fusion polypeptide includes an AsCas12a open reading frame, a nuclear localization signal, optionally an amino acid linker and optionally an affinity tag. 
     In a seventeenth aspect, a method of performing genome editing in a eukaryotic cell is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising a CRISPR-associated protein of according to the sixteenth aspect. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    depicts multiple recombinant forms of Cas12a yields a spectrum of editing efficiencies. A series of recombinant Cas12a proteins with differing composition and arrangement of NLS sequences, purification tags, and linkers (A-M; corresponding to SEQ ID NOs.:18-30) were cloned and purified to homogeneity. The resulting purified Cas12a derivatives were delivered into HEK293 cells by electroporation complexed to RNA guides that target the HPRT-38186 (SEQ ID NO.:1) and HPRT-38228 loci (SEQ ID NO.:2). DNA was isolated from genome editing experiments 48 hr later, and editing efficiencies were determined by PCR amplification of edited loci using HPRT-FWD (SEQ ID NO.:3) and HPRT-REV (SEQ ID NO.:4) primers and the Alt-R Genome Editing Detection Kit (Integrated DNA Technologies). The following abbreviations apply for the illustrated constructs: V5 refers to V5 epitope tag (SEQ ID NO.: 485); SV40 refers to a nuclear localization signal from simian virus SV40 large tumor antigen (SEQ ID NO.: 475); Cas12a refers to a Cas12a coding sequence; HIS refers to a hexahistidine tag (SEQ ID NO.: 487); OpT refers to an optimized nuclear localization signal (SEQ ID NO.: 477); aNLS refers to an alternative nuclear localization signal(SEQ ID NO.: 479); BIP1 refers to a first bipartite nuclear localization signal (SEQ ID NO.: 481); and BIP2 refers to a second bipartite nuclear localization signal (SEQ ID NO.: 483). The arrows provided in the constructs depict transcriptional start sites for mRNA transcripts originating from the DNA. 
         FIG.  2    shows exemplary results of M537R and F870L mutations with enhanced the cleavage activity of Cpf1 in a bacterial-based activity assay. The screening  E. coli  strains were transformed with Cpf1 expression vectors and the crRNA targeting HPRT-38346 site on the toxin expression plasmid. The apparent activity of Cpf1 for TTTT or TTTC PAM can be estimated by the number of survived colonies under arabinose selection when equivalent amount of plasmids is delivered. Clearly, both mutations increased the survival rate at TTTC and TTTT PAM sites, indicating an improved cleavage activity over the WT-Cpf1. 
         FIG.  3 A  shows an exemplary SDS-PAGE analysis of AsCpf1 variants used in the in vitro cleavage assay and subsequent genome editing in human cell lines. Indicated quantity of protein was loaded, and no difference was observed comparing to the WT-Cpf1. These results demonstrate M537R and F870L mutations can increase the in vitro cleavage activity of Cpf1 at non-conical TTTT PAM site while maintaining high activity at canonical TTTV site. 
         FIG.  3 B  shows exemplary DNA cleavage activities of Cpf1 variants at HPRT-38346 site with TTTC or TTTT PAM. Both variants resulted in a higher percentage of DNA cleavage at TTTT PAM site than WT-Cpf1. These results demonstrate M537R and F870L mutations can increase the in vitro cleavage activity of Cpf1 at non-conical TTTT PAM site while maintaining high activity at canonical TTTV site. 
         FIG.  4    shows a summary of results showing exemplary results of M537R and F870L mutations having broadly enhanced the genomic targeting efficiency of AsCpf1 at TTTN PAM sites in human cell line. The genomic targeting efficiencies of Cpf1 variants were tested in a human cell line model using T7 endonuclease I assay (T7EI). Twenty-four crRNAs targeting the CTNNB1 gene with TTTN PAMs were synthesized, assembled with Cpf1 variants as RNP complex, and delivered by nucleofection (Lonza). The genomic DNA was collected 48 hours post-delivery to assess the formation of indels by T7EI. Not only enabled DNA cleavage at all TTTT PAM sites that many were not targetable by WT-Cpf1, the reported variants, particularly the double-mutant (M537R/F870L), broadly enhanced the targeting efficiency of Cpf1 at 22 of 24 tested sites regardless of PAM sequence. 
         FIG.  5 A  shows exemplary correlation of relative survival rate of M537R/F870L-AsCas12a under condition 1 (X-axis) vs. relative survival rate of M537R/F870L-AsCas12a condition 2 (Y-axis). Consistent phenotype measurement was obtained (ρ˜0.7). 
         FIG.  5 B  shows exemplary correlation of relative survival rate of M537R/F870L-AsCas12a under condition 1 (X-axis) vs. relative survival rate of WT-AsCas12a under condition 3 (Y-axis). Consistent phenotype measurement was obtained (ρ˜0.7). 
         FIG.  5 C  shows exemplary correlation of relative survival rate of M537R/F870L-AsCas12a under condition 2 (X-axis) vs. relative survival rate of WT-AsCas12a under condition 2 (Y-axis). Consistent phenotype measurement was obtained (ρ˜0.7). 
         FIG.  5 D  shows exemplary variant scores of phenotype (relative survival rate) of single point mutations of a selected number of AsCas12a at positions 537 and 870 under conditions 1 and 2. 
         FIG.  5 E  shows exemplary variant scores of phenotype (relative survival rate) of single point mutations of a selected number of AsCas12a at positions 537 and 870 under conditions 1 and 2.  FIGS.  5 D and  5 E  show that M537R and F870L are the optimal substitutions at respective positions, which is consistent with the result of our previous screening and mutant characterization. 
         FIG.  5 F  shows exemplary variant scores of phenotype (relative survival rate) of single point mutations of a selected number of AsCas12a at positions 505, 510, 569 and 599 under conditions 1, 2 and 3. 
         FIG.  6 A  shows survival rate of  E. coli  resulting from DNA cleavage activity of WT-AsCas12a at TTTT PAM. The cleavage activity of AsCas12a variants at TTTT PAM site was measured by bacterial-based activity assay. The petri dish plated with the initial bacterial plating is shown on the left, while the petri dish having the surviving bacterial colonies is shown on the right. The survival of  E. coli  under selection is dependent on the success cleavage of a toxin-expressing plasmid containing a TTTT PAM site. 
         FIG.  6 B  shows survival rate of  E. coli  resulting from DNA cleavage activity of L505K-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  6 A . 
         FIG.  6 C  shows survival rate of  E. coli  resulting from DNA cleavage activity of S510L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  6 A . 
         FIG.  6 D  shows survival rate of  E. coli  resulting from DNA cleavage activity of M537R-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  6 A . 
         FIG.  6 E  shows survival rate of  E. coli  resulting from DNA cleavage activity of P569D-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  6 A . 
         FIG.  6 F  shows survival rate of  E. coli  resulting from DNA cleavage activity of P599G-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  6 A . 
         FIG.  7 A  shows survival rate of  E. coli  resulting from DNA cleavage activity of M537R/F870L-AsCas12a at TTTT PAM. The cleavage activity of M537R/F870L-AsCas12a variants at TTTT PAM site was measured by bacterial-based activity assay. The petri dish plated with the initial bacterial plating is shown on the left, while the petri dish having the surviving bacterial colonies is shown on the right. The survival of  E. coli  under selection is dependent on the success cleavage of a toxin-expressing plasmid containing a TTTT PAM site. 
         FIG.  7 B  shows survival rate of  E. coli  resulting from DNA cleavage activity of L505K/M537R/F870L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  7 A . 
         FIG.  7 C  shows survival rate of  E. coli  resulting from DNA cleavage activity of M537R/F870L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  7 A . 
         FIG.  7 D  shows survival rate of  E. coli  resulting from DNA cleavage activity of P569D/M537R/F870L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  7 A . 
         FIG.  7 E  shows survival rate of  E. coli  resulting from DNA cleavage activity of P599G/M537R/F870L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  7 A . 
         FIG.  7 F  shows survival rate of  E. coli  resulting from DNA cleavage activity of S510L/M537R/F870L-AsCas12a variant at TTTT PAM. The presentation of petri dishes and experimental details are as set forth in  FIG.  7 A . 
     
    
    
     DETAILED DESCRIPTION 
     The present invention concerns compositions of Cas12a variants and methods to enhance the utility of Cas12a and variants thereof for expression in eukaryotic cells. 
     Definitions 
     When introducing elements of aspects of the disclosure or particular embodiments, the articles “a,” “an,” “the,” and “said” are intended to mean that there are one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. The term “or” means any one member of a particular list and also includes any combination of members of that list, unless otherwise specified. 
     As intended herein, the terms “substantially,” “approximately,” and “about” and similar terms are intended to have a broad meaning in harmony with the common and accepted usage in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the invention as recited in the appended claims. 
     Definitions pertaining to certain terms and phrases applicable herein may be found in related US patents and publications, such as U.S. patent application Ser. Nos. 14/975,709, 15/299,549, 15/299,590, 15/299,593, 15/881,684, 15/729,491, 15/821,736, 15/964,041, 15/839,817, 15/839,820, 62/716,138, and U.S. Pat. No. 9,840,702. 
     The term “substantially purified,” as applied to a composition, refers to a composition having at least 90% purity or greater, including 90% purity, 95% purity, 99% purity and greater than 99% purity. 
     The adjective “isolated,” when modifying a composition, such as a polynucleotide, a polypeptide or a ribonucleoprotein complex refers to a substantially purified composition, or in the case of a ribonucleoprotein complex, at least one component being a substantially purified component. In further respect to an isolated ribonucleoprotein complex, preferably all components are substantially purified. 
     The terms “nucleic acid” and “polynucleotide” are interchangeable have the same meaning. 
     The terms “amino acid sequence,” “polypeptide,” and “protein” are interchangeable have the same meaning. 
     The term “affinity tag” refers to a ligand that permits detection and/or selection of an oligonucleotide sequence to which the ligand is attached. For the purposes of this disclosure, a bait may include an affinity tag. In particular, the affinity tag is positioned typically at either or both the N′-terminus and/or C′-terminus of a polypeptide through the use of conventional chemical coupling technology or recombinant DNA technology. Exemplary affinity tags include biotin, digoxigenin, streptavidin, polyhistine (for example, (His 6 )), glutathione-S-transferase (GST), HaloTag®, AviTag, Calmodulin-tag, polyglutamate tag, FLAG-tag, HA-tag, Myc-tag, S-tag, SBP-tag, Softag 3, V5 tag, Xpress tag, a hapten, among others. 
     The term “eukaryotic cell,” includes those cells of or derived from a particular organism, such as a plant or a mammal, including but not limited to human, or non-human eukaryote or animal or mammal as herein discussed, e.g., mouse, rat, rabbit, dog, livestock, or non-human mammal or primate. In some embodiments, processes for modifying the germ line genetic identity of human beings and/or processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes, may be excluded. Preferred human cells include cells derived from somatic cells and germ line cells. Exemplary somatic cells include cells from every major organ and tissue system, including the immune system and hematopoietic system. 
     As set forth herein, the Conditions 1, 2 and 3 refer to different combinations of background strain and the amounts of gRNA introduced in the background strain before selection of the variants. Condition 1 is a M537R/F870L background that includes an introduced amount of gRNA (100 pmol per 10 microliter transformation/plating experiment) in which variants were selected. Condition 2 is a M537R/F870L background that includes an introduced amount of gRNA (50 pmol per 10 microliter transformation/plating experiment) in which variants were selected. Condition 3 is a Wild-type AsCpf1 background that includes an introduced amount of gRNA (200 pmol per 10 microliter transformation/plating experiment) in which variants were selected. 
     Cas12a Polypeptides Having Eukaryotic Nuclear Localization Signals 
     Since Cas12a is a bacterial protein, it has no native targeting mechanism to reach the eukaryotic nucleus, where the target DNA resides. 
     To more efficiently target proteins to the eukaryotic nucleus, short protein sequences called nuclear localization signals (NLS) are commonly added to the amino- or carboxy-terminal ends of a given open reading frame. NLSs are recognized by import proteins on the eukaryotic nuclear envelope that first bind to the nuclear membrane, and subsequently permit pore translocation into the nucleus by an energy-dependent process. While recombinant protein tags like an NLS can greatly improve localization, any addition of exogenous amino acid sequences stands a reasonable chance of perturbing protein function. As such, discovering a recombinant Cas12a protein sequence that facilitates the highest amount of nuclear delivery without negatively affecting its activity will ultimately result in the most potent Cas12a genome editing solution, which is non-trivial and highly desirable. 
     To improve nuclear delivery of Cas12a without perturbing its function, several different recombinant versions of Cas12a were constructed in which the identity, location, and number of protein tags (NLS, hexahistidine tag (an exemplary affinity tag)) were varied. Whereas hexahistidine and V5 tags were added to Cas12a constructs to aid in protein purification and/or detection, the NLS tags were added to assist in delivery to the eukaryotic nucleus. Domain-breaking linker sequences were also varied in composition and location to empirically determine the best arrangement and context of tagged sequences. All constructs were first expressed in  E. coli , and recombinant Cas12a proteins were purified with immobilized metal affinity chromatography (IMAC) followed by ion exchange chromatography as described previously. 
     AsCpf1 Polypeptide Variants Having Novel Cleavage Activities 
     Amino acid substitutions in AsCpf1 that enhance the cleavage activity at both canonical (TTTV) and non-canonical (TTTT) PAM sites using a bacterial screening approach are described. This screen contained two components: i) a toxin plasmid encoding an arabinose-inducible cell proliferation toxin and a CRISPR/Cpf1 on-target cleavage site (HPRT-38346) with TTTT PAM, and ii) a chloramphenicol resistance plasmid containing a randomly-mutagenized region within the AsCpf1 sequence (˜5 mutations per kb). The screen was performed as follows:  E. coli  BW25141(λDE3) was transformed with the toxin plasmid containing the HPRT-38346 target site in the absence of arabinose, where the toxin is not produced and cell survival is permitted. Cells with stably replicating toxin plasmid are then transformed with the AsCpf1 expression plasmid and crRNA targeting HPRT-38346, and then cells were plated on media containing both chloramphenicol and arabinose. Bacteria that grew were those that i) successfully transformed with the AsCpf1 expression plasmid, ii) expressed sufficient AsCpf1 variant to cleave the toxin plasmid at HPRT-38346 site using TTTT PAM. The AsCpf1 expression plasmids within the survived cells were recovered and used in the subsequent round of selection. After multiple rounds of selection, the identities of enriched AsCpf1 variants were determined by DNA sequencing, and carried forward for analysis in mammalian cells. 
     The disclosure provides following two novel point mutations and the combination in the AsCpf1 gene that enhances the cleavage activity: M537R and F870L. The cleavage activity of individual mutant was first tested in a bacterial-based activity assay. Next, purified proteins were further tested in vitro and in human cell lines. In summary, both substitutions significantly enhanced the DNA cleavage activity of Cpf1 at TTTT PAM sites in all assays. Further, the combination of M537R and F870L broadly enhanced the targeting efficiency of AsCpf1 in human cell line. Overall, the present invention identifies novel amino-acid positions in the AsCpf1 gene that can be mutated to improve its cleavage activity at all TTTN (N=A/G/C/T) PAM sites. 
     As explained in the Background section, the prior art consists of using wild-type Cpf1 protein or two variants that are compatible with TYCV and TATV PAMs. As stated previously, these variants have limited utility due to the complex and mutually exclusive requirement of PAM sequence. Further, none of the variants showed any improved cleavage activity at TTTT PAM, which is unfortunately more frequent than other TTTV PAM sites (V=G/A/C) throughout the human genome. In contrast, not only enabling efficient cleavage at TTTT PAM, the mutations reported in this invention (M537R and F870L) broadly enhanced the cleavage activity of Cpf1 at canonical TTTV sites tested in human cell line. Together, the enhanced activity and broadened PAM flexibility (TTTN) of this invention makes it a superior CRISPR enzyme, which could directly replace the current wild-type Cpf1 in the application genomic editing. 
     High-Throughput Generation of AsCas12a Variants Having Cleavage Activity Towards a TTTT PAM-Containing Target Site. 
     The phenotype of all point mutations in the following regions of AsCas12a: 499-640 and 840-913 in the bacterial screening measuring the DNA cleavage activity at non-canonical TTTT PAM is described. Three sets of screening were performed to measure the phenotype of each point mutation, in the background of both WT-AsCas12a and M537R/F870L-AsCas12a. Cross-comparison of three datasets revealed consistent phenotype measurements, which enabled us to isolate novel AsCas12a variants with enhanced activity beyond M537R and F870L. 
     The high-throughput characterization of Cas12a activity at a TTTT PAM site provided the functional consequence of every possible single amino acid change within targeted region. The unbiased strategy of the present invention enables one to identify a large collection of mutants to further enhance the cleavage activity of AsCas12a over our previous invention (M537R/F870L). 
     To improve the coverage and efficiency of the screening, we generated an AsCas12a deep-scanning mutagenesis library containing all possible point mutations on the protein level in the targeted regions (490-640 and 840-913), with most clones contain only one mutation. This type of library allowed us to directly evaluate the phenotype of each point mutation, by measuring their relative survival rates over the reference protein in the bacterial screen. Briefly, the screening strain harboring the toxin plasmid was transformed with AsCas12a library with TTTT PAM-containing target site on the toxin plasmid. After transformation, cells were plated on selective media. AsCas12a expression plasmids carried by the survived  E. coli  cells were extracted and purified. Both input and selected plasmid libraries were PCR amplified, and sequenced on Illumina MiSeq with 1-2 million reads per library. The frequencies of each AsCas12a variant in both libraries were determined using Enrich 2, and normalized to the reference protein (WT or M537R/F870L). The relative survival rate of each point mutation over reference was calculated as the ratio of normalized frequency between selected and input library. Since the degree of cell survival is indicative of the DNA cleavage activity of each AsCas12a variant, any variants with higher survival rate than the reference protein would be those with enhanced activity at TTTT PAM. 
     As presented herein, codon-optimized Cas12a polypeptides are provided, including codon-optimized Cas12a polypeptides for CRISPR ribonucleoprotein complexes. An example of a codon-optimized sequence, is in this instance a sequence optimized for expression in eukaryotes, e.g., humans (i.e., being optimized for expression in humans), or for another eukaryote, animal or mammal as herein discussed. Whilst this is preferred, it will be appreciated that other examples are possible and codon optimization for a host species other than human, or for codon optimization for specific organs is known. In some embodiments, an enzyme coding sequence encoding a CRISPR Cas12a polypeptide is a codon optimized for expression in particular cells, such as eukaryotic cells. The eukaryotic cells may be those of or derived from a particular organism, such as a plant or a mammal, including but not limited to human, or non-human eukaryote or animal or mammal as herein discussed, e.g., mouse, rat, rabbit, dog, livestock, or non-human mammal or primate. In some embodiments, processes for modifying the germ line genetic identity of human beings and/or processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes, may be excluded. 
     Preferred human cells include cells derived from somatic cells and germ line cells. Exemplary somatic cells include cells from every major organ and tissue system, including the immune system and hematopoietic system. 
     In general, codon optimization refers to a process of modifying a nucleic acid sequence for enhanced expression in the host cells of interest by replacing at least one codon (e.g. about or more than about 1, 2, 3, 4, 5, 10, 15, 20, 25, 50, or more codons) of the native sequence with codons that are more frequently or most frequently used in the genes of that host cell while maintaining the native amino acid sequence. Various species exhibit particular bias for certain codons of a particular amino acid. Codon bias (differences in codon usage between organisms) often correlates with the efficiency of translation of messenger RNA (mRNA), which is in turn believed to be dependent on, among other things, the properties of the codons being translated and the availability of particular transfer RNA (tRNA) molecules. The predominance of selected tRNAs in a cell is generally a reflection of the codons used most frequently in peptide synthesis. Accordingly, genes can be tailored for optimal gene expression in a given organism based on codon optimization. Codon usage tables are readily available. See Nakamura, Y., et al. “Codon usage tabulated from the international DNA sequence databases: status for the year 2000” Nucl. Acids Res. 28:292 (2000). Computer algorithms for codon optimizing a particular sequence for expression in a particular host cell are also available, such as Gene Forge (Aptagen; Jacobus, Pa.), are also available. In some embodiments, one or more codons (e.g. 1, 2, 3, 4, 5, 10, 15, 20, 25, 50, or more, or all codons) in a sequence encoding a Cas12a correspond to the most frequently used codon for a particular amino acid. 
     Additionally, codon-optimized Cas12a polypeptides are provided, including codon-optimized Cas12a polypeptides for CRISPR ribonucleoprotein complexes, wherein the Cas12a polypeptide sequence optimized for expression in prokaryotes, such as bacteria (e.g.,  E. coli ). 
     Applications 
     This invention is useful for either basic research or therapeutic fields for any CRISPR/Cas12a DNA cleavage and/or gene editing experiments or treatments. The superior activity of these recombinant variants could be applied to Cas12a from any species or potentially any CRISPR enzyme. 
     In a first aspect, A CRISPR-associated protein comprising a polypeptide encoding a variant of AsCpf1 is provided. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). In a first respect, the CRISPR-associated protein corresponds to a variant of AsCpf1 is M537R. In a second respect, the CRISPR-associated protein corresponds to a variant of AsCpf1 is F870L (SEQ ID NO.: 473). In a third respect, the CRISPR-associated protein corresponds to a variant of AsCpf1 is M537R/F870L (SEQ ID NO.: 465). 
     In a second aspect, a CRISPR ribonucleoprotein complex is provided. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein including a polypeptide encoding a variant of AsCpf1. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). In a first respect, the CRISPR ribonucleoprotein complex includes the variant of AsCpf1 being M537R. In a second respect, the CRISPR ribonucleoprotein complex includes the variant of AsCpf1 being F870L (SEQ ID NO.: 473). In a third respect, the CRISPR ribonucleoprotein complex includes the variant of AsCpf1 being M537R/F870L (SEQ ID NO.: 465). 
     In a third aspect, a method of increasing efficiency of gene editing at TTTN PAM sites in a cell with a CRISPR ribonucleoprotein complex is provided. The method includes the step of contacting a cell with the CRISPR ribonucleoprotein complex. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein including a polypeptide encoding a variant of AsCpf1. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473) and M537R/F870L (SEQ ID NO.: 465). In a first respect, the TTTN PAM sites consists of one selected form the group of TTTA, TTTT and TTTC PAM sites. 
     In a fourth aspect, a kit includes a guide RNA and a CRISPR-associated protein is provided. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCpf1. The variant of AsCpf1 is selected from the group consisting of M537R (SEQ ID NO.: 472), F870L (SEQ ID NO.: 473), and M537R/F870L (SEQ ID NO.: 465). In a first respect, the variant of AsCpf1 is M537R. In a second respect, the variant of AsCpf1 is F870L (SEQ ID NO.: 473). In a third respect, the variant of AsCpf1 is M537R/F870L (SEQ ID NO.: 465). 
     In a fifth aspect, a CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. In a first respect, the variant of AsCas12a is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the variant of AsCas12a, as described in the first aspect or the foregoing first respect of the first aspect, further comprises mutations of M537R/F870L (SEQ ID NO.: 465). 
     In a sixth aspect, a CRISPR ribonucleoprotein complex is provided. The CRISPR ribonucleoprotein complex includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. In a first respect, the variant of AsCas12a is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the variant of AsCas12a, as described in the second aspect or the foregoing first respect of the second aspect, further comprises mutations of M537R/F870L (SEQ ID NO.: 465). 
     In a seventh aspect, a method of increasing efficiency of gene editing at non-canonical TTTT PAM sites in a cell with a CRISPR ribonucleoprotein complex is provided. The method includes a step of contacting a cell with the CRISPR ribonucleoprotein complex that includes a guide RNA and a CRISPR-associated protein. The CRISPR-associated protein includes a polypeptide encoding a variant of AsCas12a, wherein the variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. In a first respect, the variant of AsCas12a is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the variant of AsCas12a, as described in the third aspect or the foregoing first respect of the third aspect, further comprises mutations of M537R/F870L (SEQ ID NO.: 465). 
     In an eighth aspect, a kit including a guide RNA and a CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a is provided. The variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. In a first respect, the variant of AsCas12a is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the variant of AsCas12a, as described in the fourth aspect or the foregoing first respect of the fourth aspect, further comprises mutations of M537R/F870L (SEQ ID NO.: 465). 
     In a ninth aspect, a nucleic acid encoding a CRISPR-associated protein comprising a polypeptide encoding a variant of AsCas12a is provided. The variant of AsCas12a is selected from the group consisting of at least one variant amino acid selected from amino acid positions 499-640 and 840-913, provided that the variant AsCas12a provides an improvement in CRISPR/AsCas12a-associated nuclease activity at non-canonical TTTT PAM sites. Highly preferred nucleic acids encoding a CRISPR-associated protein include isolated nucleic acids encoding a CRISPR-associated protein. In a first respect, the variant of AsCas12a is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the variant of AsCas12a further includes mutations of M537R/F870L (SEQ ID NO.: 465). In a third respect, the nucleic acid is operably linked to suitable transcription elements to express the nucleic acid. In a fourth respect, the nucleic acid is DNA or RNA. 
     In a tenth aspect, a polynucleotide sequence encoding a Cas12a polypeptide is provided. The polynucleotide sequence includes one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In an eleventh aspect, an amino acid sequence encoding a Cas12a polypeptide is provided. The amino acid sequence includes one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a twelfth aspect, a CAS endonuclease system comprising an expression cassette encoding a polynucleotide sequence encoding a Cas12a polypeptide is provided. The includes one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In a thirteenth aspect, CAS endonuclease system comprising an amino acid sequence encoding a Cas12a polypeptide is provided The amino acid sequence includes one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a fourteenth aspect, a method of performing genome editing in a eukaryotic cells is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising an expression cassette encoding a polynucleotide sequence encoding a Cas12a polypeptide, comprising one member selected from the group consisting of SEQ ID NOs.: 5-17. 
     In a fifteenth aspect, a method of performing genome editing in a eukaryotic cell is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising an amino acid sequence encoding a Cas12a polypeptide comprising one member selected from the group consisting of SEQ ID NOs.: 18-30. 
     In a sixteenth aspect, an CRISPR-associated protein comprising a fusion polypeptide is provided. The fusion polypeptide includes an AsCas12a open reading frame, a nuclear localization signal, optionally an amino acid linker and optionally an affinity tag. Highly preferred CRISPR-associated proteins include isolated CRISPR-associated proteins. In a first respect, the AsCas12a open reading frame is selected from the group consisting of SEQ ID NOs.: 59-245. In a second respect, the nuclear localization signal is selected from SEQ ID NOs.: 475, 477, 479, 481 and 483. In a third respect, the CRISPR-associated protein is encoded by SEQ ID NOs.: 488-491. In a fourth respect, the CRISPR-associated protein is selected from SEQ ID NOs.: 492 and 493. 
     In a seventeenth aspect, a method of performing genome editing in a eukaryotic cell is provided. The method includes the step of introducing an CAS endonuclease system into the eukaryotic cell, said CAS endonuclease system comprising an CRISPR-associated protein of according to the sixteenth aspect. Highly preferred CRISPR-associated proteins include isolated CRISPR-associated proteins. 
     EXAMPLES 
     Example 1. Recombinant Cas12a Proteins with Varying Tags/Linker Sequences Yield a Spectrum of Editing Efficiencies 
     The following Example demonstrates that recombinant Cas12a proteins with only modest changes in tag sequences at the amino- and carboxy-termini results in proteins that demonstrate a wide range of editing efficiencies in human cells ( FIG.  1   ). 
     Briefly, the method of site directed mutagenesis (SDM) was employed to create the expression constructs having As Cas12a coding sequences with different nuclear localization signals (NLS&#39;s). Site directed mutagenesis was performed by designing complimentary primers that encompass the desired nucleotide base change(s), along with flanking plasmid vector sequence, wherein each flanking region has a melting temperature (T m ) of at least 60° C. A polymerase chain reaction (PCR) run was then performed using standard cycling conditions for a total of 16 cycles. The restriction enzyme, DPN I, was added to digest away the starting plasmid vector material so only the new product containing the base changes remain. After DPN I treatment, a small amount of the PCR product was transformed into competent  E. coli  cells, recovered in SOC media and plated onto kanamycin resistance Luria Broth (LB) agar plates. Colonies were screened using the Sanger sequencing method to verify correct base changes in selected clones. 
     The results indicate that the ideal sequence and placement of NLS sequences on Cas12a is not obvious, and that a highly efficient Cas12a genome editing solution must be empirically determined as was done in this study. Proteins were tested using guides that target the HPRT-38186 (SEQ ID NO.:1) and HPRT-38228 (SEQ ID NO.:2) loci in human cells. SEQ ID NOs.: 1-4 are depicted in Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Sequence of oligonucleotides used as 
               
               
                 crRNAs or PCR primers. 
               
            
           
           
               
               
               
            
               
                 Name 
                 Sequence 
                 SEQ ID NO. 
               
               
                   
               
               
                 HPRT- 
                 rUrArArUrUrUrCrUrArCrUrCrUrUr 
                 SEQ ID NO. 1 
               
               
                 38186-S 
                 GrUrArGrArUrUrArArUrGrCrCr 
                   
               
               
                   
                 CrUrGrUrArGrUrCrUrCrUrCrUrG 
                   
               
               
                   
               
               
                 HPRT- 
                 rUrArArUrUrUrCrUrArCrUrCrUr 
                 SEQ ID NO. 2 
               
               
                 38228-S 
                 UrGrUrArGrArUrUrArArUrUrArAr 
                   
               
               
                   
                 CrArGrCrUrUrGrCrUrGrGrUrGrA 
                   
               
               
                   
               
               
                 HPRT-FWD 
                 AAGAATGTTGTGATAAAAGGTGATGCT 
                 SEQ ID NO. 3 
               
               
                   
               
               
                 HPRT-REV 
                 GAGGCAGAAGTCCCATGGATGTGT 
                 SEQ ID NO. 4 
               
               
                   
               
            
           
         
       
     
     The following nucleotide sequences that encode preferred Cas12a polypeptides of this Example are depicted below: 
     
       
         
           
               
               
            
               
                 SEQ ID NO.: 5 
                   
               
               
                 ATGGGCAGCAGCAGCAGCGGCCTGGTGCCGCGCGGCAGCCATATGGCTAGCATGACTGGT 
                   
               
               
                   
               
               
                 GGACAGCAAATGGGTCGGGATCCAGGTAAACCGATTCCGAATCCGCTGCTGGGTCTGGATAGCACCGCACCG 
               
               
                   
               
               
                 AAAAAAAAACGTAAAGTTGGTATTCATGGTGTTCCGGCAGCAACCCAGTTTGAAGGTTTCACCAATCTGTATC 
               
               
                   
               
               
                 AGGTTAGCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTT 
               
               
                   
               
               
                 CATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACC 
               
               
                   
               
               
                 TATGCAGATCAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCA 
               
               
                   
               
               
                 AAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATT 
               
               
                   
               
               
                 ATTTCATTGGTCGTACCGATAATCTGACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTT 
               
               
                   
               
               
                 AAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCAC 
               
               
                   
               
               
                 TGCTGCGTAGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCA 
               
               
                   
               
               
                 GAAGATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACA 
               
               
                   
               
               
                 TTTTTACCCGTCTGATTACCGCAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATC 
               
               
                   
               
               
                 TTTGTTAGCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGA 
               
               
                   
               
               
                 TCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGT 
               
               
                   
               
               
                 GCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGC 
               
               
                   
               
               
                 TGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGT 
               
               
                   
               
               
                 GATTCAGAGCTTTTGCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTT 
               
               
                   
               
               
                 AACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACT 
               
               
                   
               
               
                 GTGTGATCATTGGGATACCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACC 
               
               
                   
               
               
                 AAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCA 
               
               
                   
               
               
                 GCCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTG 
               
               
                   
               
               
                 CTGGGTCTGTATCATCTGCTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCAC 
               
               
                   
               
               
                 GTCTGACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAA 
               
               
                   
               
               
                 AAAACCGTATAGCGTCGAAAAATTCAAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAAT 
               
               
                   
               
               
                 AAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGA 
               
               
                   
               
               
                 AAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACG 
               
               
                   
               
               
                 ACTATTTTCCGGATGCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCA 
               
               
                   
               
               
                 GACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGAT 
               
               
                   
               
               
                 CTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGT 
               
               
                   
               
               
                 TATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTAT 
               
               
                   
               
               
                 CGATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTAC 
               
               
                   
               
               
                 CTGTTCCAGATCTACAATAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGAC 
               
               
                   
               
               
                 CGGTCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGT 
               
               
                   
               
               
                 CCGAAAAGCCGTATGAAACGTATGGCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAG 
               
               
                   
               
               
                 AAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGA 
               
               
                   
               
               
                 GTGATGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCG 
               
               
                   
               
               
                 TTTTACCAGCGACAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAAT 
               
               
                   
               
               
                 TTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACG 
               
               
                   
               
               
                 TAACCTGATTTATATCACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGC 
               
               
                   
               
               
                 AGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTG 
               
               
                   
               
               
                 TTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCA 
               
               
                   
               
               
                 CTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAA 
               
               
                   
               
               
                 GCAGTTTATCAGCAGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCA 
               
               
                   
               
               
                 GAGCGGATTTCTGTTTTATGTTCCGGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGT 
               
               
                   
               
               
                 TTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGAC 
               
               
                   
               
               
                 GTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTT 
               
               
                   
               
               
                 TATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCA 
               
               
                   
               
               
                 GGTAAACGTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATG 
               
               
                   
               
               
                 AACTGATCGCACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGA 
               
               
                   
               
               
                 AAATGATGATAGCCATGCAATTGATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAAT 
               
               
                   
               
               
                 GCAGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCA 
               
               
                   
               
               
                 GAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCT 
               
               
                   
               
               
                 GAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATAT 
               
               
                   
               
               
                 CCAAGAACTGCGTAACCCTAAAAAAAAACGCAAAGTGAAGCTTGCGGCCGCACTCGAGCACCACCACCACCA 
               
               
                   
               
               
                 CCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 6 
                   
               
               
                 ATGGGCAGCAGCAGCAGCGGCCTGGTGCCGCGCGGCAGCCATATGGCTAGCATGACTGGT 
                   
               
               
                   
               
               
                 GGACAGCAAATGGGTCGGGATCCAGCACCGAAAAAAAAACGTAAAGTTGGTATTCATGGTGTTCCGGCAGCA 
               
               
                   
               
               
                 ACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAA 
               
               
                   
               
               
                 AACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACT 
               
               
                   
               
               
                 GAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAA 
               
               
                   
               
               
                 AATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAA 
               
               
                   
               
               
                 CAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCAATTAACAA 
               
               
                   
               
               
                 ACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGC 
               
               
                   
               
               
                 ACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCACCTATTTCAGCGGCTT 
               
               
                   
               
               
                 TTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGAT 
               
               
                   
               
               
                 AATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAGCCTGCGTGAACA 
               
               
                   
               
               
                 TTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTT 
               
               
                   
               
               
                 ACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGAAGCAGG 
               
               
                   
               
               
                 CACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATT 
               
               
                   
               
               
                 ATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATT 
               
               
                   
               
               
                 CTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAACGCTGCTGCGCAATGAA 
               
               
                   
               
               
                 AATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAGCCA 
               
               
                   
               
               
                 CAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATGCCCTGTATGAACGT 
               
               
                   
               
               
                 CGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAG 
               
               
                   
               
               
                 GATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGC 
               
               
                   
               
               
                 GAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAA 
               
               
                   
               
               
                 GAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGTTTGCAGTTGATGAAA 
               
               
                   
               
               
                 GCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCT 
               
               
                   
               
               
                 TTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAACTTTCAGATG 
               
               
                   
               
               
                 CCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGC 
               
               
                   
               
               
                 CTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAA 
               
               
                   
               
               
                 ACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAATGATTCCGAAATGTAGCA 
               
               
                   
               
               
                 CCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTGAA 
               
               
                   
               
               
                 CCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCGCA 
               
               
                   
               
               
                 TATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATT 
               
               
                   
               
               
                 TTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCT 
               
               
                   
               
               
                 GGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATC 
               
               
                   
               
               
                 ATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTTGCCAAAGGCCATCATG 
               
               
                   
               
               
                 GCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAA 
               
               
                   
               
               
                 ACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCGTCTGGGTGA 
               
               
                   
               
               
                 AAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGA 
               
               
                   
               
               
                 TTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAA 
               
               
                   
               
               
                 GAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTTCATGTGCCGATTACCCT 
               
               
                   
               
               
                 GAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCAGAA 
               
               
                   
               
               
                 ACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGATAGCACCGGCAAAAT 
               
               
                   
               
               
                 CCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGA 
               
               
                   
               
               
                 ACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCA 
               
               
                   
               
               
                 GGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCT 
               
               
                   
               
               
                 TTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAAAATGCTGATTGACAAACT 
               
               
                   
               
               
                 GAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGAT 
               
               
                   
               
               
                 CAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCACCGTATACGAGCA 
               
               
                   
               
               
                 AAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACA 
               
               
                   
               
               
                 TTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATC 
               
               
                   
               
               
                 GCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAAC 
               
               
                   
               
               
                 ACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCATCGTTTCA 
               
               
                   
               
               
                 CCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAGAAAGGTATTGTTTTTCG 
               
               
                   
               
               
                 TGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGCACTG 
               
               
                   
               
               
                 ATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTG 
               
               
                   
               
               
                 ATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAA 
               
               
                   
               
               
                 CGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACCCTAAAAAAAAACGCAAAGTGAA 
               
               
                   
               
               
                 GCTTGCGGCCGCACTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 7 
                   
               
               
                 ATGCCGAAAAAAAAACGCAAAGTGGGTATTCATGGTGTTCCGGCAGCAACCCAGTTTGAA 
                   
               
               
                   
               
               
                 GGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAAC 
               
               
                   
               
               
                 ATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTA 
               
               
                   
               
               
                 TCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGC 
               
               
                   
               
               
                 AGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCAACCTA 
               
               
                   
               
               
                 TCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCAATTAACAAACGTCACGCCG 
               
               
                   
               
               
                 AAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACCAC 
               
               
                   
               
               
                 CACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAGAATC 
               
               
                   
               
               
                 GCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAA 
               
               
                   
               
               
                 ATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAGCCTGCGTGAACATTTTGAAAACG 
               
               
                   
               
               
                 TTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTG 
               
               
                   
               
               
                 CTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGAAGCAGGCACCGAAAAA 
               
               
                   
               
               
                 ATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCC 
               
               
                   
               
               
                 TGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGAAGAA 
               
               
                   
               
               
                 TTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGG 
               
               
                   
               
               
                 AAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAGCCACAAAAAACT 
               
               
                   
               
               
                 GGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATGCCCTGTATGAACGTCGTATTAGC 
               
               
                   
               
               
                 GAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGATATTAAT 
               
               
                   
               
               
                 CTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAAATTCTG 
               
               
                   
               
               
                 TCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTG 
               
               
                   
               
               
                 AAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGTTTGCAGTTGATGAAAGCAATGAA 
               
               
                   
               
               
                 GTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACA 
               
               
                   
               
               
                 AAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAACTTTCAGATGCCGACCCT 
               
               
                   
               
               
                 GGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTA 
               
               
                   
               
               
                 TCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGA 
               
               
                   
               
               
                 AGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTG 
               
               
                   
               
               
                 AAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTGAACCGCTGGA 
               
               
                   
               
               
                 AATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCGCATATGCAAA 
               
               
                   
               
               
                 AAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTCTGAGC 
               
               
                   
               
               
                 AAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGGCGAA 
               
               
                   
               
               
                 TATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTTGCCAAAGGCCATCATGGCAAACC 
               
               
                   
               
               
                 GAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAAT 
               
               
                   
               
               
                 GGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCGTCTGGGTGAAAAAATG 
               
               
                   
               
               
                 CTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGA 
               
               
                   
               
               
                 ACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTAG 
               
               
                   
               
               
                 CCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCA 
               
               
                   
               
               
                 GGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCAGAAACGCCGATT 
               
               
                   
               
               
                 ATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGATAGCACCGGCAAAATCCTGGAAC 
               
               
                   
               
               
                 AGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAACGTGTTG 
               
               
                   
               
               
                 CAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATTCA 
               
               
                   
               
               
                 TGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGC 
               
               
                   
               
               
                 AAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAAAATGCTGATTGACAAACTGAATTGC 
               
               
                   
               
               
                 CTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTA 
               
               
                   
               
               
                 CCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCACCGTATACGAGCAAAATTGA 
               
               
                   
               
               
                 TCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGG 
               
               
                   
               
               
                 AAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCGCAATCTG 
               
               
                   
               
               
                 AGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCG 
               
               
                   
               
               
                 ATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGT 
               
               
                   
               
               
                 TATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCT 
               
               
                   
               
               
                 CAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGCACTGATTCGTAG 
               
               
                   
               
               
                 CGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTGATCTGAAT 
               
               
                   
               
               
                 GGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGCATATCATA 
               
               
                   
               
               
                 TTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTA 
               
               
                   
               
               
                 GCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACCCGAAAAAAAAACGCAAAGTGCTCGAGCACC 
               
               
                   
               
               
                 ACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 8 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACCCGAAA 
               
               
                   
               
               
                 AAAAAACGCAAAGTGCTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 9 
                   
               
               
                 ATGGGCAGCAGCCATCATCATCATCATCACAGCAGCGGCCTGGTGCCGCGCGGCAGCCATA 
                   
               
               
                   
               
               
                 TGGCTAGCATGACTGGTGGACAGCAAATGGGTCGGGATCCAACCCAGTTTGAAGGTTTCACCAATCTGTATCA 
               
               
                   
               
               
                 GGTTAGCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTC 
               
               
                   
               
               
                 ATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCT 
               
               
                   
               
               
                 ATGCAGATCAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCA 
               
               
                   
               
               
                 AAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATT 
               
               
                   
               
               
                 ATTTCATTGGTCGTACCGATAATCTGACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTT 
               
               
                   
               
               
                 AAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCAC 
               
               
                   
               
               
                 TGCTGCGTAGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCA 
               
               
                   
               
               
                 GAAGATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACA 
               
               
                   
               
               
                 TTTTTACCCGTCTGATTACCGCAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATC 
               
               
                   
               
               
                 TTTGTTAGCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGA 
               
               
                   
               
               
                 TCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGT 
               
               
                   
               
               
                 GCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGC 
               
               
                   
               
               
                 TGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGT 
               
               
                   
               
               
                 GATTCAGAGCTTTTGCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTT 
               
               
                   
               
               
                 AACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACT 
               
               
                   
               
               
                 GTGTGATCATTGGGATACCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACC 
               
               
                   
               
               
                 AAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCA 
               
               
                   
               
               
                 GCCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTG 
               
               
                   
               
               
                 CTGGGTCTGTATCATCTGCTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCAC 
               
               
                   
               
               
                 GTCTGACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAA 
               
               
                   
               
               
                 AAAACCGTATAGCGTCGAAAAATTCAAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAAT 
               
               
                   
               
               
                 AAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGA 
               
               
                   
               
               
                 AAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACG 
               
               
                   
               
               
                 ACTATTTTCCGGATGCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCA 
               
               
                   
               
               
                 GACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGAT 
               
               
                   
               
               
                 CTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGT 
               
               
                   
               
               
                 TATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTAT 
               
               
                   
               
               
                 CGATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTAC 
               
               
                   
               
               
                 CTGTTCCAGATCTACAATAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGAC 
               
               
                   
               
               
                 CGGTCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGT 
               
               
                   
               
               
                 CCGAAAAGCCGTATGAAACGTATGGCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAG 
               
               
                   
               
               
                 AAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGA 
               
               
                   
               
               
                 GTGATGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCG 
               
               
                   
               
               
                 TTTTACCAGCGACAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAAT 
               
               
                   
               
               
                 TTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACG 
               
               
                   
               
               
                 TAACCTGATTTATATCACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGC 
               
               
                   
               
               
                 AGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTG 
               
               
                   
               
               
                 TTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCA 
               
               
                   
               
               
                 CTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAA 
               
               
                   
               
               
                 GCAGTTTATCAGCAGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCA 
               
               
                   
               
               
                 GAGCGGATTTCTGTTTTATGTTCCGGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGT 
               
               
                   
               
               
                 TTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGAC 
               
               
                   
               
               
                 GTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTT 
               
               
                   
               
               
                 TATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCA 
               
               
                   
               
               
                 GGTAAACGTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATG 
               
               
                   
               
               
                 AACTGATCGCACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGA 
               
               
                   
               
               
                 AAATGATGATAGCCATGCAATTGATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAAT 
               
               
                   
               
               
                 GCAGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCA 
               
               
                   
               
               
                 GAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCT 
               
               
                   
               
               
                 GAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATAT 
               
               
                   
               
               
                 CCAAGAACTGCGTAACGGTCGTAGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAA 
               
               
                   
               
               
                 AAAGAAACGTAAAGTTGGTGGTAGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTG 
               
               
                   
               
               
                 GTGGCTCTGGTGGTAGCCTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 10 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGT 
               
               
                   
               
               
                 AGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAACGTAAAGTTGGTGG 
               
               
                   
               
               
                 TAGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGCCTCG 
               
               
                   
               
               
                 AGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 11 
                   
               
               
                 ATGGGCAGCAGCAGCAGCGGCCTGGTGCCGCGCGGCAGCCATATGGCTAGCATGACTGGT 
                   
               
               
                   
               
               
                 GGACAGCAAATGGGTCGGGATCCAACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGC 
               
               
                   
               
               
                 GTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAG 
               
               
                   
               
               
                 CACGTAACGATCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCT 
               
               
                   
               
               
                 GCAGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGA 
               
               
                   
               
               
                 AACCCGTAATGCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCG 
               
               
                   
               
               
                 ATAATCTGACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAA 
               
               
                   
               
               
                 TGGCAAAGTTCTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGAT 
               
               
                   
               
               
                 AAATTCACCACCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCG 
               
               
                   
               
               
                 CAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATT 
               
               
                   
               
               
                 ACCGCAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCA 
               
               
                   
               
               
                 TTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTG 
               
               
                   
               
               
                 CTGGGTGGTATTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATT 
               
               
                   
               
               
                 CAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCT 
               
               
                   
               
               
                 GAGCGATCGTAATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGC 
               
               
                   
               
               
                 AAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCA 
               
               
                   
               
               
                 TTGATCTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGAT 
               
               
                   
               
               
                 ACCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAA 
               
               
                   
               
               
                 AAAGTTCAGCGCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTG 
               
               
                   
               
               
                 TCAGAAGCATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGA 
               
               
                   
               
               
                 CCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATC 
               
               
                   
               
               
                 TGCTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAA 
               
               
                   
               
               
                 ACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTC 
               
               
                   
               
               
                 GAAAAATTCAAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAAC 
               
               
                   
               
               
                 GGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAG 
               
               
                   
               
               
                 CGCTGAGCTTTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGC 
               
               
                   
               
               
                 AGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCG 
               
               
                   
               
               
                 ATTCTGCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAA 
               
               
                   
               
               
                 AAGAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGT 
               
               
                   
               
               
                 GTAAATGGATTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCT 
               
               
                   
               
               
                 GCGTCCGAGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGC 
               
               
                   
               
               
                 TTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACA 
               
               
                   
               
               
                 ATAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCT 
               
               
                   
               
               
                 GAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGA 
               
               
                   
               
               
                 AACGTATGGCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGG 
               
               
                   
               
               
                 ATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGC 
               
               
                   
               
               
                 CCTGCTGCCGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAA 
               
               
                   
               
               
                 TTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAA 
               
               
                   
               
               
                 TGCATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATC 
               
               
                   
               
               
                 ACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGA 
               
               
                   
               
               
                 AAAAACTGGATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAG 
               
               
                   
               
               
                 ACCTGAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGT 
               
               
                   
               
               
                 TGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAG 
               
               
                   
               
               
                 TTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGT 
               
               
                   
               
               
                 GTTCTGAATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTT 
               
               
                   
               
               
                 TTATGTTCCGGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCA 
               
               
                   
               
               
                 TCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGA 
               
               
                   
               
               
                 TTTCATCCTGCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGG 
               
               
                   
               
               
                 ATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGT 
               
               
                   
               
               
                 TCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGC 
               
               
                   
               
               
                 TGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCA 
               
               
                   
               
               
                 TGCAATTGATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAA 
               
               
                   
               
               
                 GATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCC 
               
               
                   
               
               
                 GATGGATGCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGA 
               
               
                   
               
               
                 AAGCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAA 
               
               
                   
               
               
                 CGGTCGTAGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAACGTAAAGT 
               
               
                   
               
               
                 TGGTGGTAGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTA 
               
               
                   
               
               
                 GCCTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 12 
                   
               
               
                 ATGCCGCCTCCGAAACGTCCGCGTCTGGATGGTATCCACGGAGTCCCAGCAGCCACCCAGT 
                   
               
               
                   
               
               
                 TTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCTG 
               
               
                   
               
               
                 AAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTGAAACCG 
               
               
                   
               
               
                 ATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAAAATCTGA 
               
               
                   
               
               
                 GCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCAA 
               
               
                   
               
               
                 CCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCAATTAACAAACGTCAC 
               
               
                   
               
               
                 GCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTA 
               
               
                   
               
               
                 CCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAG 
               
               
                   
               
               
                 AATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCC 
               
               
                   
               
               
                 CGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAGCCTGCGTGAACATTTTGAA 
               
               
                   
               
               
                 AACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCA 
               
               
                   
               
               
                 GCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGAAGCAGGCACCGA 
               
               
                   
               
               
                 AAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATTATTGCA 
               
               
                   
               
               
                 AGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGA 
               
               
                   
               
               
                 AGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAACGCTGCTGCGCAATGAAAATGTT 
               
               
                   
               
               
                 CTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAGCCACAAAA 
               
               
                   
               
               
                 AACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATGCCCTGTATGAACGTCGTAT 
               
               
                   
               
               
                 TAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGATAT 
               
               
                   
               
               
                 TAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAAAT 
               
               
                   
               
               
                 TCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAAT 
               
               
                   
               
               
                 CCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGTTTGCAGTTGATGAAAGCAAT 
               
               
                   
               
               
                 GAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATA 
               
               
                   
               
               
                 ACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAACTTTCAGATGCCGAC 
               
               
                   
               
               
                 CCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTA 
               
               
                   
               
               
                 TTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAG 
               
               
                   
               
               
                 TGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAATGATTCCGAAATGTAGCACCCAG 
               
               
                   
               
               
                 CTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTGAACCGCT 
               
               
                   
               
               
                 GGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCGCATATGC 
               
               
                   
               
               
                 AAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTCTG 
               
               
                   
               
               
                 AGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGGC 
               
               
                   
               
               
                 GAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGG 
               
               
                   
               
               
                 ACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTTGCCAAAGGCCATCATGGCAA 
               
               
                   
               
               
                 ACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGA 
               
               
                   
               
               
                 ATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCGTCTGGGTGAAAAAA 
               
               
                   
               
               
                 TGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGATTATGT 
               
               
                   
               
               
                 GAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTT 
               
               
                   
               
               
                 AGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTTCATGTGCCGATTACCCTGAATTAT 
               
               
                   
               
               
                 CAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCAGAAACGCCG 
               
               
                   
               
               
                 ATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGATAGCACCGGCAAAATCCTGGA 
               
               
                   
               
               
                 ACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAACGTGT 
               
               
                   
               
               
                 TGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATT 
               
               
                   
               
               
                 CATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAA 
               
               
                   
               
               
                 GCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAAAATGCTGATTGACAAACTGAATT 
               
               
                   
               
               
                 GCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTT 
               
               
                   
               
               
                 TACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCACCGTATACGAGCAAAATT 
               
               
                   
               
               
                 GATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCT 
               
               
                   
               
               
                 GGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCGCAATC 
               
               
                   
               
               
                 TGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTT 
               
               
                   
               
               
                 CGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGT 
               
               
                   
               
               
                 CGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATG 
               
               
                   
               
               
                 GCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGCACTGATTCG 
               
               
                   
               
               
                 TAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTGATCTG 
               
               
                   
               
               
                 AATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGCATATC 
               
               
                   
               
               
                 ATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCA 
               
               
                   
               
               
                 TTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGTAGCAGTGATGATGAAGCAACCG 
               
               
                   
               
               
                 CAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAACGTAAAGTTGGTGGTAGCGGTGGTTCAGGTGGTAGT 
               
               
                   
               
               
                 GGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGCCTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 13 
                   
               
               
                 ATGAGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAA 
                   
               
               
                   
               
               
                 CGTAAAGTTGGTATCCACGGAGTCCCAGCAGCCACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCA 
               
               
                   
               
               
                 AAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGA 
               
               
                   
               
               
                 GGATAAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGAT 
               
               
                   
               
               
                 CAGTGTCTGCAGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAA 
               
               
                   
               
               
                 ACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTG 
               
               
                   
               
               
                 GTCGTACCGATAATCTGACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGA 
               
               
                   
               
               
                 ACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGT 
               
               
                   
               
               
                 AGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATAT 
               
               
                   
               
               
                 TAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCC 
               
               
                   
               
               
                 GTCTGATTACCGCAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGC 
               
               
                   
               
               
                 ACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAA 
               
               
                   
               
               
                 CCAACTGCTGGGTGGTATTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCT 
               
               
                   
               
               
                 GGCCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAAC 
               
               
                   
               
               
                 AAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAG 
               
               
                   
               
               
                 CTTTTGCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTG 
               
               
                   
               
               
                 AATAGCATTGATCTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCA 
               
               
                   
               
               
                 TTGGGATACCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCG 
               
               
                   
               
               
                 AAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAA 
               
               
                   
               
               
                 GAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGC 
               
               
                   
               
               
                 TGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGT 
               
               
                   
               
               
                 ATCATCTGCTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGG 
               
               
                   
               
               
                 CATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTAT 
               
               
                   
               
               
                 AGCGTCGAAAAATTCAAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAA 
               
               
                   
               
               
                 AACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTT 
               
               
                   
               
               
                 ATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCC 
               
               
                   
               
               
                 GGATGCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACC 
               
               
                   
               
               
                 ACCCCGATTCTGCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACC 
               
               
                   
               
               
                 CGGAAAAAGAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAA 
               
               
                   
               
               
                 GCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGA 
               
               
                   
               
               
                 GCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCA 
               
               
                   
               
               
                 TATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAG 
               
               
                   
               
               
                 ATCTACAATAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTT 
               
               
                   
               
               
                 TAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGC 
               
               
                   
               
               
                 CGTATGAAACGTATGGCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCG 
               
               
                   
               
               
                 ATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAG 
               
               
                   
               
               
                 CACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAG 
               
               
                   
               
               
                 CGACAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGC 
               
               
                   
               
               
                 GTGTTAATGCATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGAT 
               
               
                   
               
               
                 TTATATCACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATT 
               
               
                   
               
               
                 ACCAGAAAAAACTGGATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAA 
               
               
                   
               
               
                 TTAAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGC 
               
               
                   
               
               
                 CGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTAT 
               
               
                   
               
               
                 CAGCAGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTT 
               
               
                   
               
               
                 GGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGAT 
               
               
                   
               
               
                 TTCTGTTTTATGTTCCGGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGG 
               
               
                   
               
               
                 AAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAAC 
               
               
                   
               
               
                 GGGTGATTTCATCCTGCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTG 
               
               
                   
               
               
                 CATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAAC 
               
               
                   
               
               
                 GTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATC 
               
               
                   
               
               
                 GCACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATG 
               
               
                   
               
               
                 ATAGCCATGCAATTGATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAAC 
               
               
                   
               
               
                 CGGTGAAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGG 
               
               
                   
               
               
                 AATGGCCGATGGATGCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACC 
               
               
                   
               
               
                 TGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAAC 
               
               
                   
               
               
                 TGCGTAACGGTCGTAGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAAC 
               
               
                   
               
               
                 GTAAAGTTGGTGGTAGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCT 
               
               
                   
               
               
                 GGTGGTAGCCTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 14 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGT 
               
               
                   
               
               
                 AAACGTCCGGCAGCAACCAAAAAAGCAGGTCAGGCAAAAAAGAAAAAAGGTGGTAGCGGTGGTTCAGGTG 
               
               
                   
               
               
                 GTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGCCTCGAGCACCACCACCACCACC 
               
               
                   
               
               
                 ACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 15 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGT 
               
               
                   
               
               
                 AAACGTACCGCAGATGGTAGCGAATTTGAAAGCCCGAAAAAAAAGCGTAAGGTGGAAGGTGGTAGCGGTGG 
               
               
                   
               
               
                 TTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGCCTCGAGCACCACCA 
               
               
                   
               
               
                 CCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 16 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGT 
               
               
                   
               
               
                 AGCAGTGATGATGAAGCAACCGCAGATAGCCAGCATGCAGCACCGCCTAAAAAGAAACGTAAAGTTGGTGG 
               
               
                   
               
               
                 TAGCGGCGGTAGTAAACGTACCGCAGATGGTAGCGAATTTGAAAGCCCGAAAAAAAAGCGTAAGGTGGAAG 
               
               
                   
               
               
                 GTGGTAGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGC 
               
               
                   
               
               
                 CTCGAGCACCACCACCACCACCACTGA 
               
               
                   
               
               
                 SEQ ID NO.: 17 
                   
               
               
                 ATGACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCTGCGTTTTGAACT 
                   
               
               
                   
               
               
                 GATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAAGCACGTAACGA 
               
               
                   
               
               
                 TCACTACAAAGAACTGAAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCTGGTT 
               
               
                   
               
               
                 CAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCTGAC 
               
               
                   
               
               
                 CGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAGCCGAACTGTTTAATGGCAAAGTT 
               
               
                   
               
               
                 CTGAAACAGCTGGGCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCA 
               
               
                   
               
               
                 CCTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGCAATTCCGCA 
               
               
                   
               
               
                 TCGTATTGTGCAGGATAATTTCCCGAAATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTC 
               
               
                   
               
               
                 CGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTA 
               
               
                   
               
               
                 TTAGCCGTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGGCCATTCAGAAAAATG 
               
               
                   
               
               
                 ATGAAACCGCACATATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGT 
               
               
                   
               
               
                 AATACCCTGAGCTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCAAATACAAAA 
               
               
                   
               
               
                 CGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTGAC 
               
               
                   
               
               
                 CCACATCTTTATCAGCCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATTACCAAAAGCGCGAAAGAAAAAGTTCAGC 
               
               
                   
               
               
                 GCAGTCTGAAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAGCAT 
               
               
                   
               
               
                 TTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGCCGACCACCCTGAA 
               
               
                   
               
               
                 AAAACAAGAAGAAAAAGAAATCCTGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTG 
               
               
                   
               
               
                 GTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTC 
               
               
                   
               
               
                 AAACTGAACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAACAACGGTGCCATC 
               
               
                   
               
               
                 CTGTTCGTGAAAAATGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCT 
               
               
                   
               
               
                 TTGAACCGACGGAAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCAGCCAAAAT 
               
               
                   
               
               
                 GATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCTGA 
               
               
                   
               
               
                 GCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGA 
               
               
                   
               
               
                 AAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGAAGCGCTGTGTAAATGGA 
               
               
                   
               
               
                 TTGATTTCACCCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCGAGC 
               
               
                   
               
               
                 AGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAGCGTA 
               
               
                   
               
               
                 TTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTT 
               
               
                   
               
               
                 TGCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATG 
               
               
                   
               
               
                 GCACATCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGATCCCGGATACACTG 
               
               
                   
               
               
                 TATCAAGAACTGTATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGC 
               
               
                   
               
               
                 CGAATGTTATTACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAAATTCTTTTTT 
               
               
                   
               
               
                 CATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCATATC 
               
               
                   
               
               
                 TGAAAGAACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGTTTGATTACCAGAAAAAACTG 
               
               
                   
               
               
                 GATAATCGCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCTGAAA 
               
               
                   
               
               
                 CAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGTGCTGG 
               
               
                   
               
               
                 AAAACCTGAATTTTGGCTTTAAAAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCC 
               
               
                   
               
               
                 GGCACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAAC 
               
               
                   
               
               
                 CATGAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCT 
               
               
                   
               
               
                 GCACTTTAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCTGCATGGGATATTGTGT 
               
               
                   
               
               
                 TTGAGAAAAACGAAACACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGAT 
               
               
                   
               
               
                 TGAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGAG 
               
               
                   
               
               
                 AAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTG 
               
               
                   
               
               
                 ATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTGAAGATTACAT 
               
               
                   
               
               
                 TAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGGAATGGCCGATGGAT 
               
               
                   
               
               
                 GCAGATGCAAATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGCAAA 
               
               
                   
               
               
                 GATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAACGGTCGT 
               
               
                   
               
               
                 AAACGTCCGGCAGCAACCAAAAAAGCAGGTCAGGCAAAAAAGAAAAAAGGTGGTAGCGGCGGTAGTAAAC 
               
               
                   
               
               
                 GTACCGCAGATGGTAGCGAATTTGAAAGCCCGAAAAAAAAGCGTAAGGTGGAAGGTGGTAGCGGTGGTTCA 
               
               
                   
               
               
                 GGTGGTAGTGGCGGTAGTGGTGGCTCAGGGGGTTCTGGTGGCTCTGGTGGTAGCCTCGAGCACCACCACCA 
               
               
                   
               
               
                 CCACCACTGA 
               
            
           
         
       
     
     The following amino acid sequences of preferred Cas12a polypeptides are depicted below. 
     
       
         
           
               
            
               
                 SEQ ID NO.: 18 
               
               
                 MGSSSSGLVPRGSHMASMTGGQQMGRDPGKPIPNPLLGLDSTAPKKKRKV 
               
               
                   
               
               
                 GIHGVPAATQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKAR 
               
               
                   
               
               
                 NDHYKELKPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRN 
               
               
                   
               
               
                 ALIEEQATYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVL 
               
               
                   
               
               
                 KQLGTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRI 
               
               
                   
               
               
                 VQDNFPKFKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSF 
               
               
                   
               
               
                 PFYNQLLTQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAH 
               
               
                   
               
               
                 IIASLPHRFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNE 
               
               
                   
               
               
                 NVLETAEALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERR 
               
               
                   
               
               
                 ISELTGKITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEIL 
               
               
                   
               
               
                 SHAHAALDQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVD 
               
               
                   
               
               
                 PEFSARLTGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASG 
               
               
                   
               
               
                 WDVNKEKNNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKM 
               
               
                   
               
               
                 YYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIY 
               
               
                   
               
               
                 DLNNPEKEPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSI 
               
               
                   
               
               
                 DLSSLRPSSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLF 
               
               
                   
               
               
                 QIYNKDFAKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKS 
               
               
                   
               
               
                 RMKRMAHRLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEAR 
               
               
                   
               
               
                 ALLPNVITKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVN 
               
               
                   
               
               
                 AYLKEHPETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKK 
               
               
                   
               
               
                 LDNREKERVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLE 
               
               
                   
               
               
                 NLNFGFKSKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPY 
               
               
                   
               
               
                 QLTDQFTSFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHES 
               
               
                   
               
               
                 RKHFLEGFDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKN 
               
               
                   
               
               
                 ETQFDAKGTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVF 
               
               
                   
               
               
                 RDGSNILPKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRD 
               
               
                   
               
               
                 LNGVCFDSRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGI 
               
               
                   
               
               
                 SNQDWLAYIQELRNPKKKRKVKLAAALEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 19 
               
               
                 MGSSSSGLVPRGSHMASMTGGQQMGRDPAPKKKRKVGIHGVPAATQFEGF 
               
               
                   
               
               
                 TNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKELKPIIDRI 
               
               
                   
               
               
                 YKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAIH 
               
               
                   
               
               
                 DYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVTTTEHENA 
               
               
                   
               
               
                 LLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPKFKENCHI 
               
               
                   
               
               
                 FTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLLTQTQIDL 
               
               
                   
               
               
                 YNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPHRFIPLFK 
               
               
                   
               
               
                 QILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAEALFNELN 
               
               
                   
               
               
                 SIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGKITKSAKE 
               
               
                   
               
               
                 KVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAALDQPLPTT 
               
               
                   
               
               
                 LKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARLTGIKLEM 
               
               
                   
               
               
                 EPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEKNNGAILF 
               
               
                   
               
               
                 VKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPDAAKMIPK 
               
               
                   
               
               
                 CSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEKEPKKFQT 
               
               
                   
               
               
                 AYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKDL 
               
               
                   
               
               
                 GEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDFAKGHHGK 
               
               
                   
               
               
                 PNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAHRLGEKML 
               
               
                   
               
               
                 NKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVITKEVSHE 
               
               
                   
               
               
                 IIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHPETPIIGI 
               
               
                   
               
               
                 DRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKERVAARQA 
               
               
                   
               
               
                 WSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFKSKRTGIA 
               
               
                   
               
               
                 EKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFTSFAKMGT 
               
               
                   
               
               
                 QSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHYD 
               
               
                   
               
               
                 VKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAKGTPFIAG 
               
               
                   
               
               
                 KRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNILPKLLEND 
               
               
                   
               
               
                 DSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFDSRFQNPE 
               
               
                   
               
               
                 WPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLAYIQELRN 
               
               
                   
               
               
                 PKKKRKVKLAAALEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 20 
               
               
                 MPKKKRKVGIHGVPAATQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQG 
               
               
                   
               
               
                 FIEEDKARNDHYKELKPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRK 
               
               
                   
               
               
                 EKTEETRNALIEEQATYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKA 
               
               
                   
               
               
                 ELFNGKVLKQLGTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDI 
               
               
                   
               
               
                 STAIPHRIVQDNFPKFKENCHIFTRLITAVPSLREHFENVKKAIGIFVST 
               
               
                   
               
               
                 SIEEVFSFPFYNQLLTQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAI 
               
               
                   
               
               
                 QKNDETAHIIASLPHRFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCK 
               
               
                   
               
               
                 YKTLLRNENVLETAEALFNELNSIDLTHIFISHKKLETISSALCDHWDTL 
               
               
                   
               
               
                 RNALYERRISELTGKITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAF 
               
               
                   
               
               
                 KQKTSEILSHAHAALDQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFA 
               
               
                   
               
               
                 VDESNEVDPEFSARLTGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNF 
               
               
                   
               
               
                 QMPTLASGWDVNKEKNNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEK 
               
               
                   
               
               
                 TSEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEP 
               
               
                   
               
               
                 LEITKEIYDLNNPEKEPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLS 
               
               
                   
               
               
                 KYTKTTSIDLSSLRPSSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAV 
               
               
                   
               
               
                 ETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQA 
               
               
                   
               
               
                 ELFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLS 
               
               
                   
               
               
                 HDLSDEARALLPNVITKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSP 
               
               
                   
               
               
                 SKFNQRVNAYLKEHPETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTI 
               
               
                   
               
               
                 QQFDYQKKLDNREKERVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIH 
               
               
                   
               
               
                 YQAVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEK 
               
               
                   
               
               
                 VGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVW 
               
               
                   
               
               
                 KTIKNHESRKHFLEGFDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPA 
               
               
                   
               
               
                 WDIVFEKNETQFDAKGTPFIAGKRIVPVIENHRFTGRYRDLYPANELIAL 
               
               
                   
               
               
                 LEEKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSVLQMRNSNAATGED 
               
               
                   
               
               
                 YINSPVRDLNGVCFDSRFQNPEWPMDADANGAYHIALKGQLLLNHLKESK 
               
               
                   
               
               
                 DLKLQNGISNQDWLAYIQELRNPKKKRKVLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 21 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNPKKKRKVLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 22 
               
               
                 MGSSHHHHHHSSGLVPRGSHMASMTGGQQMGRDPTQFEGFTNLYQVSKTL 
               
               
                   
               
               
                 RFELIPQGKTLKHIQEQGFIEEDKARNDHYKELKPIIDRIYKTYADQCLQ 
               
               
                   
               
               
                 LVQLDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAIHDYFIGRTDNL 
               
               
                   
               
               
                 TDAINKRHAEIYKGLFKAELFNGKVLKQLGTVTTTEHENALLRSFDKFTT 
               
               
                   
               
               
                 YFSGFYENRKNVFSAEDISTAIPHRIVQDNFPKFKENCHIFTRLITAVPS 
               
               
                   
               
               
                 LREHFENVKKAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGGISR 
               
               
                   
               
               
                 EAGTEKIKGLNEVLNLAIQKNDETAHIIASLPHRFIPLFKQILSDRNTLS 
               
               
                   
               
               
                 FILEEFKSDEEVIQSFCKYKTLLRNENVLETAEALFNELNSIDLTHIFIS 
               
               
                   
               
               
                 HKKLETISSALCDHWDTLRNALYERRISELTGKITKSAKEKVQRSLKHED 
               
               
                   
               
               
                 INLQEIISAAGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEIL 
               
               
                   
               
               
                 KSQLDSLLGLYHLLDWFAVDESNEVDPEFSARLTGIKLEMEPSLSFYNKA 
               
               
                   
               
               
                 RNYATKKPYSVEKFKLNFQMPTLASGWDVNKEKNNGAILFVKNGLYYLGI 
               
               
                   
               
               
                 MPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPDAAKMIPKCSTQLKAVTA 
               
               
                   
               
               
                 HFQTHTTPILLSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQK 
               
               
                   
               
               
                 GYREALCKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKDLGEYYAELNPL 
               
               
                   
               
               
                 LYHISFQRIAEKEIMDAVETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTG 
               
               
                   
               
               
                 LFSPENLAKTSIKLNGQAELFYRPKSRMKRMAHRLGEKMLNKKLKDQKTP 
               
               
                   
               
               
                 IPDTLYQELYDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTSD 
               
               
                   
               
               
                 KFFFHVPITLNYQAANSPSKFNQRVNAYLKEHPETPIIGIDRGERNLIYI 
               
               
                   
               
               
                 TVIDSTGKILEQRSLNTIQQFDYQKKLDNREKERVAARQAWSVVGTIKDL 
               
               
                   
               
               
                 KQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFKSKRTGIAEKAVYQQFEK 
               
               
                   
               
               
                 MLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPA 
               
               
                   
               
               
                 PYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHYDVKTGDFILHF 
               
               
                   
               
               
                 KMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAKGTPFIAGKRIVPVIENH 
               
               
                   
               
               
                 RFTGRYRDLYPANELIALLEEKGIVFRDGSNILPKLLENDDSHAIDTMVA 
               
               
                   
               
               
                 LIRSVLQMRNSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANGA 
               
               
                   
               
               
                 YHIALKGQLLLNHLKESKDLKLQNGISNQDWLAYIQELRNGRSSDDEATA 
               
               
                   
               
               
                 DSQHAAPPKKKRKVGGSGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 23 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNGRSSDDEATADSQHAAPPKKKRKVGGSGGSGGSGGSGGSGGSG 
               
               
                   
               
               
                 GSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 24 
               
               
                 MGSSSSGLVPRGSHMASMTGGQQMGRDPTQFEGFTNLYQVSKTLRFELIP 
               
               
                   
               
               
                 QGKTLKHIQEQGFIEEDKARNDHYKELKPIIDRIYKTYADQCLQLVQLDW 
               
               
                   
               
               
                 ENLSAAIDSYRKEKTEETRNALIEEQATYRNAIHDYFIGRTDNLTDAINK 
               
               
                   
               
               
                 RHAEIYKGLFKAELFNGKVLKQLGTVTTTEHENALLRSFDKFTTYFSGFY 
               
               
                   
               
               
                 ENRKNVFSAEDISTAIPHRIVQDNFPKFKENCHIFTRLITAVPSLREHFE 
               
               
                   
               
               
                 NVKKAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGGISREAGTEK 
               
               
                   
               
               
                 IKGLNEVLNLAIQKNDETAHIIASLPHRFIPLFKQILSDRNTLSFILEEF 
               
               
                   
               
               
                 KSDEEVIQSFCKYKTLLRNENVLETAEALFNELNSIDLTHIFISHKKLET 
               
               
                   
               
               
                 ISSALCDHWDTLRNALYERRISELTGKITKSAKEKVQRSLKHEDINLQEI 
               
               
                   
               
               
                 ISAAGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEILKSQLDS 
               
               
                   
               
               
                 LLGLYHLLDWFAVDESNEVDPEFSARLTGIKLEMEPSLSFYNKARNYATK 
               
               
                   
               
               
                 KPYSVEKFKLNFQMPTLASGWDVNKEKNNGAILFVKNGLYYLGIMPKQKG 
               
               
                   
               
               
                 RYKALSFEPTEKTSEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQTHT 
               
               
                   
               
               
                 TPILLSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQKGYREAL 
               
               
                   
               
               
                 CKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKDLGEYYAELNPLLYHISF 
               
               
                   
               
               
                 QRIAEKEIMDAVETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTGLFSPEN 
               
               
                   
               
               
                 LAKTSIKLNGQAELFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPDTLY 
               
               
                   
               
               
                 QELYDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTSDKFFFHV 
               
               
                   
               
               
                 PITLNYQAANSPSKFNQRVNAYLKEHPETPIIGIDRGERNLIYITVIDST 
               
               
                   
               
               
                 GKILEQRSLNTIQQFDYQKKLDNREKERVAARQAWSVVGTIKDLKQGYLS 
               
               
                   
               
               
                 QVIHEIVDLMIHYQAVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLIDKL 
               
               
                   
               
               
                 NCLVLKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPAPYTSKI 
               
               
                   
               
               
                 DPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHYDVKTGDFILHFKMNRNL 
               
               
                   
               
               
                 SFQRGLPGFMPAWDIVFEKNETQFDAKGTPFIAGKRIVPVIENHRFTGRY 
               
               
                   
               
               
                 RDLYPANELIALLEEKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSVL 
               
               
                   
               
               
                 QMRNSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANGAYHIALK 
               
               
                   
               
               
                 GQLLLNHLKESKDLKLQNGISNQDWLAYIQELRNGRSSDDEATADSQHAA 
               
               
                   
               
               
                 PPKKKRKVGGSGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 25 
               
               
                 MPPPKRPRLDGIHGVPAATQFEGFTNLYQVSKTLRFELIPQGKTLKHIQE 
               
               
                   
               
               
                 QGFIEEDKARNDHYKELKPIIDRIYKTYADQCLQLVQLDWENLSAAIDSY 
               
               
                   
               
               
                 RKEKTEETRNALIEEQATYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLF 
               
               
                   
               
               
                 KAELFNGKVLKQLGTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAE 
               
               
                   
               
               
                 DISTAIPHRIVQDNFPKFKENCHIFTRLITAVPSLREHFENVKKAIGIFV 
               
               
                   
               
               
                 STSIEEVFSFPFYNQLLTQTQIDLYNQLLGGISREAGTEKIKGLNEVLNL 
               
               
                   
               
               
                 AIQKNDETAHIIASLPHRFIPLFKQILSDRNTLSFILEEFKSDEEVIQSF 
               
               
                   
               
               
                 CKYKTLLRNENVLETAEALFNELNSIDLTHIFISHKKLETISSALCDHWD 
               
               
                   
               
               
                 TLRNALYERRISELTGKITKSAKEKVQRSLKHEDINLQEIISAAGKELSE 
               
               
                   
               
               
                 AFKQKTSEILSHAHAALDQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDW 
               
               
                   
               
               
                 FAVDESNEVDPEFSARLTGIKLEMEPSLSFYNKARNYATKKPYSVEKFKL 
               
               
                   
               
               
                 NFQMPTLASGWDVNKEKNNGAILFVKNGLYYLGIMPKQKGRYKALSFEPT 
               
               
                   
               
               
                 EKTSEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFI 
               
               
                   
               
               
                 EPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQKGYREALCKWIDFTRDF 
               
               
                   
               
               
                 LSKYTKTTSIDLSSLRPSSQYKDLGEYYAELNPLLYHISFQRIAEKEIMD 
               
               
                   
               
               
                 AVETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNG 
               
               
                   
               
               
                 QAELFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHR 
               
               
                   
               
               
                 LSHDLSDEARALLPNVITKEVSHEIIKDRRFTSDKFFFHVPITLNYQAAN 
               
               
                   
               
               
                 SPSKFNQRVNAYLKEHPETPIIGIDRGERNLIYITVIDSTGKILEQRSLN 
               
               
                   
               
               
                 TIQQFDYQKKLDNREKERVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLM 
               
               
                   
               
               
                 IHYQAVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPA 
               
               
                   
               
               
                 EKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPF 
               
               
                   
               
               
                 VWKTIKNHESRKHFLEGFDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFM 
               
               
                   
               
               
                 PAWDIVFEKNETQFDAKGTPFIAGKRIVPVIENHRFTGRYRDLYPANELI 
               
               
                   
               
               
                 ALLEEKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSVLQMRNSNAATG 
               
               
                   
               
               
                 EDYINSPVRDLNGVCFDSRFQNPEWPMDADANGAYHIALKGQLLLNHLKE 
               
               
                   
               
               
                 SKDLKLQNGISNQDWLAYIQELRNGRSSDDEATADSQHAAPPKKKRKVGG 
               
               
                   
               
               
                 SGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 26 
               
               
                 MSSDDEATADSQHAAPPKKKRKVGIHGVPAATQFEGFTNLYQVSKTLRFE 
               
               
                   
               
               
                 LIPQGKTLKHIQEQGFIEEDKARNDHYKELKPIIDRIYKTYADQCLQLVQ 
               
               
                   
               
               
                 LDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAIHDYFIGRTDNLTDA 
               
               
                   
               
               
                 INKRHAEIYKGLFKAELFNGKVLKQLGTVTTTEHENALLRSFDKFTTYFS 
               
               
                   
               
               
                 GFYENRKNVFSAEDISTAIPHRIVQDNFPKFKENCHIFTRLITAVPSLRE 
               
               
                   
               
               
                 HFENVKKAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGGISREAG 
               
               
                   
               
               
                 TEKIKGLNEVLNLAIQKNDETAHIIASLPHRFIPLFKQILSDRNTLSFIL 
               
               
                   
               
               
                 EEFKSDEEVIQSFCKYKTLLRNENVLETAEALFNELNSIDLTHIFISHKK 
               
               
                   
               
               
                 LETISSALCDHWDTLRNALYERRISELTGKITKSAKEKVQRSLKHEDINL 
               
               
                   
               
               
                 QEIISAAGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEILKSQ 
               
               
                   
               
               
                 LDSLLGLYHLLDWFAVDESNEVDPEFSARLTGIKLEMEPSLSFYNKARNY 
               
               
                   
               
               
                 ATKKPYSVEKFKLNFQMPTLASGWDVNKEKNNGAILFVKNGLYYLGIMPK 
               
               
                   
               
               
                 QKGRYKALSFEPTEKTSEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQ 
               
               
                   
               
               
                 THTTPILLSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQKGYR 
               
               
                   
               
               
                 EALCKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKDLGEYYAELNPLLYH 
               
               
                   
               
               
                 ISFQRIAEKEIMDAVETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTGLFS 
               
               
                   
               
               
                 PENLAKTSIKLNGQAELFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPD 
               
               
                   
               
               
                 TLYQELYDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTSDKFF 
               
               
                   
               
               
                 FHVPITLNYQAANSPSKFNQRVNAYLKEHPETPIIGIDRGERNLIYITVI 
               
               
                   
               
               
                 DSTGKILEQRSLNTIQQFDYQKKLDNREKERVAARQAWSVVGTIKDLKQG 
               
               
                   
               
               
                 YLSQVIHEIVDLMIHYQAVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLI 
               
               
                   
               
               
                 DKLNCLVLKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPAPYT 
               
               
                   
               
               
                 SKIDPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHYDVKTGDFILHFKMN 
               
               
                   
               
               
                 RNLSFQRGLPGFMPAWDIVFEKNETQFDAKGTPFIAGKRIVPVIENHRFT 
               
               
                   
               
               
                 GRYRDLYPANELIALLEEKGIVFRDGSNILPKLLENDDSHAIDTMVALIR 
               
               
                   
               
               
                 SVLQMRNSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANGAYHI 
               
               
                   
               
               
                 ALKGQLLLNHLKESKDLKLQNGISNQDWLAYIQELRNGRSSDDEATADSQ 
               
               
                   
               
               
                 HAAPPKKKRKVGGSGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 27 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNGRKRPAATKKAGQAKKKKGGSGGSGGSGGSGGSGGSGGSGGSL 
               
               
                   
               
               
                 EHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 28 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNGRKRTADGSEFESPKKKRKVEGGSGGSGGSGGSGGSGGSGGSG 
               
               
                   
               
               
                 GSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 29 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNGRSSDDEATADSQHAAPPKKKRKVGGSGGSKRTADGSEFESPK 
               
               
                   
               
               
                 KKRKVEGGSGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
               
                   
               
               
                 SEQ ID NO.: 30 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRNGRKRPAATKKAGQAKKKKGGSGGSKRTADGSEFESPKKKRKVE 
               
               
                   
               
               
                 GGSGGSGGSGGSGGSGGSGGSGGSLEHHHHHH 
               
            
           
         
       
     
     Example 2. Novel Cpf1 Mutants Enhance the DNA Cleavage Activity at TTTT PAM Site in the Bacterial-Based Activity Assay 
     The following Example demonstrates the enhanced activity of the invention at both TTTT and TTTC PAM sites in a bacterial-based activity assay ( FIG.  2   ). The screening strains harboring the toxin plasmid were transformed with WT, M537R or F870L AsCpf1 expression plasmid. After recovery and IPTG induction, cells were plated on LB-Chloramphenicol media with or without arabinose. The degree of cell survival under the arabinose selection compared to the transformation input control (without arabinose) is indicative of the cleavage activity of Cpf1 variants at the HPRT-38346 protospacer on the toxin plasmid, in the context of TTTT or TTTC PAM. 
     For WT-Cpf1, the survival rate of transformed  E. coli  at TTTC is significantly higher than the TTTT PAM, which is in good agreement with the prior knowledge that the TTTT is a low activity PAM site [6] . In contrast, both M537R and F870L increased the survival rate at TTTT PAM, indicating these mutants broadened the PAM compatibility of AsCpf1 at this alternative PAM site. More importantly, the survival rate of both mutants at the canonical TTTC PAM is even higher than the WT-Cpf1, suggesting these mutants generally enhanced the performance of AsCpf1 protein at other TTTV sites as well. Given these positive results, individual AsCpf1 variant and the double mutant (M537R/F870L) were expressed and purified to determine their intrinsic cleavage activities in vitro. 
     Example 3. Novel Cpf1 Mutants Enhances the Intrinsic DNA Cleavage Activity at TTTT PAM Sites In Vitro 
     The intrinsic DNA cleavage activities of AsCpf1 variants (M537R, F870L and M537R/F870L) were compared to the wild type protein using in vitro cleavage assay. Briefly, the Cpf1-crRNA ribonucleoprotein (RNP) complex was first assembled by incubating the purified proteins ( FIG.  3 A ) with HPRT-38346 crRNA in 1×cleavage buffer (20 mM HEPES, pH 7.5, 150 mM KCl, 5 mM MgCl 2 , 10% Glycerol, and 1 mM DTT) for 15 minutes at 37° C. The cleavage reactions were initiated by titrating RNP complex (8˜500 nM) in 10 nM dsDNA substrate containing the HPRT-38346 protospacer, in the context of TTTC or TTTT PAM. Cleavage reactions at various time points were sampled and quenched by 50 mM EDTA. After removing the AsCpf1 protein by Proteanise K treatment (56° C., 30 minutes), reactions were resolved using capillary electrophoresis (Fragment Analyzer, AATI). The relative concentration of cleavage products and uncleaved dsDNA were quantified to calculate the percentage of DNA cleavage. 
     The intrinsic DNA cleavage activities of WT and Cpf1 variants at the TTTT and TTTC PAM sites were compared in  FIG.  3 B . Only a single RNP concentration (31 nM) at 20 seconds time-point was shown for simplicity. As expected, the single-nucleotide change of PAM sequence from TTTC to TTTT reduced the cleavage activity of WT-Cpf1 from ˜95% to ˜40%. Consistent with the observations in the bacterial-based activity assay, both mutants significantly increased the DNA cleavage at TTTT PAM, while maintaining high activity at TTTC PAM ( FIG.  3 B ). The double-mutant (M537R/F870L) has similar activities to the M537R in this assay. However, it is worth to note that this is likely due to the limited resolution of this particular assay, to resolve further differences among those high-activity variants. Overall, these results demonstrated that the reported mutations improved the activity of Cpf1 by enhancing the intrinsic DNA cleavage. Therefore, we anticipate that the observed benefits of these mutants will be broadly applicable and independent of the delivery methods and/or cellular contexts of the specific experiment. 
     Example 4. Novel Mutants Broadly Enhance the Targeting Efficiency of TTTN PAM Sites in Human Cell Line 
     The following Example demonstrates the ability of the invention to increase the efficiency of gene editing at TTTN PAM sites when the Cpf1-crRNA complex is delivered into cells as an RNP. 
     CRISPR/Cpf1 cellular editing experiments were performed by first forming 4 M RNP complex with purified Cpf1 protein and the Alt-R™ crRNAs in Opti-MEM for 5 min at 25° C. The targeted protospacers and PAM sequences in CTNNB1 loci are shown in Table 2. RNP complexes were then transfected into HEK293 cells by Lonza nucleofection. Experiments were performed in biological triplicate. After 48 hr at 37° C. with 5% CO 2 , adherent cells were washed with 0.1 ml PBS and lysed with 0.05 ml QuickExtract™ DNA extraction solution. Cell lysates were incubated at 65° C. for 15 min followed by heat-inactivation at 98° C. for 3 min. Crude DNA samples were then diluted 3-fold with 0.1 ml ddH 2 O and used as PCR templates. PCR primers are indicated in Table 2. PCR was used to amplify 1 kb fragments of the CTNNB1 loci using the KAPA HiFi DNA Polymerase and the following cycling parameters: 95 5:00  (98 0:20 , 64 0:15 , 72 0:30 ) repeated 29 times, 72 200 . Heteroduplexes were formed using the following cycling parameters: 95 10 ′ cooled to 85 over 1 min, 85 1:00  cooled to 75 over 1 min, 75 1:00  cooled to 65 over 1 min, 65 1:00  cooled to 55 over 1 min, 55 1:00  cooled to 45 over 1 min, 45 1:00  cooled to 35 over 1 min, 35 1:00  cooled to 25 over 1 min, 25 1:00 . Heteroduplexes were cleaved by the addition of 2U T7 Endonuclease I (New England Biolabs) for 1 hr at 37 C, and cut products were analyzed by capillary electrophoresis (Fragment Analyzer, Advanced Analytical). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Sequence of DNA target sites and primer used for 
               
               
                 PCR amplification (SEQ ID NOs.: 31-58). 
               
            
           
           
               
               
               
            
               
                 Name 
                 Sequence (5′-3′) 
                 SEQ ID NO.: 
               
               
                   
               
               
                 HPRT38346 
                   TTTT ACATAAAACTCTTTTAGGTTA 
                 SEQ ID NO.: 
               
               
                 TTTT PAM 
                   
                 31 
               
               
                   
               
               
                 HPRT38346 
                   TTTC ACATAAAACTCTTTTAGGTTA 
                 SEQ ID NO.: 
               
               
                 TTTC PAM 
                   
                 32 
               
               
                   
               
               
                 CTNNB1 
                   TTTT CCCCTCCCTGGCTTTTATTAT 
                 SEQ ID NO.: 
               
               
                 111-S 
                   
                 33 
               
               
                   
               
               
                 CTNNB1 
                   TTTC CCCTCCCTGGCTTTTATTATT 
                 SEQ ID NO.: 
               
               
                 112-S 
                   
                 34 
               
               
                   
               
               
                 CTNNB1 
                   TTTT ATTATTACAACTCTGTGCTTT 
                 SEQ ID NO.: 
               
               
                 127-S 
                   
                 35 
               
               
                   
               
               
                 CTNNB1 
                   TTTA TTATTACAACTCTGTGCTTTT 
                 SEQ ID NO.: 
               
               
                 128-S 
                   
                 36 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TCATCACCATCCTGAATATCT 
                 SEQ ID NO.: 
               
               
                 149-S 
                   
                 37 
               
               
                   
               
               
                 CTNNB1 
                   TTTT CATCACCATCCTGAATATCTA 
                 SEQ ID NO.: 
               
               
                 150-S 
                   
                 38 
               
               
                   
               
               
                 CTNNB1 
                   TTTC ATCACCATCCTGAATATCTAT 
                 SEQ ID NO.: 
               
               
                 151-S 
                   
                 39 
               
               
                   
               
               
                 CTNNB1 
                   TTTA TACTATTAATAAAAAGACATT 
                 SEQ ID NO.: 
               
               
                 184-S 
                   
                 40 
               
               
                   
               
               
                 CTNNB1 
                   TTTA TTAATAGTATAAATATTAATT 
                 SEQ ID NO.: 
               
               
                 193-AS 
                   
                 41 
               
               
                   
               
               
                 CTNNB1 
                   TTTT ATTAATAGTATAAATATTAAT 
                 SEQ ID NO.: 
               
               
                 194-AS 
                   
                 42 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TATTAATAGTATAAATATTAA 
                 SEQ ID NO.: 
               
               
                 195-AS 
                   
                 43 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TGGTAAGGAGGAGTTTTCACT 
                 SEQ ID NO.: 
               
               
                 207-S 
                   
                 44 
               
               
                   
               
               
                 CTNNB1 
                   TTTT GGTAAGGAGGAGTTTTCACTG 
                 SEQ ID NO.: 
               
               
                 208-S 
                   
                 45 
               
               
                   
               
               
                 CTNNB1 
                   TTTG GTAAGGAGGAGTTTTCACTGA 
                 SEQ ID NO.: 
               
               
                 209-S 
                   
                 46 
               
               
                   
               
               
                 CTNNB1 
                   TTTT CACTGAAGTTCAGCAGTGATG 
                 SEQ ID NO.: 
               
               
                 224-S 
                   
                 47 
               
               
                   
               
               
                 CTNNB1 
                   TTTC ACTGAAGTTCAGCAGTGATGG 
                 SEQ ID NO.: 
               
               
                 225-S 
                   
                 48 
               
               
                   
               
               
                 CTNNB1 
                   TTTC ACTAACCTGGTAAAAGAGGAT 
                 SEQ ID NO.: 
               
               
                 291-S 
                   
                 49 
               
               
                   
               
               
                 CTNNB1 
                   TTTA CCAGGTTAGTGAAACGCAGAC 
                 SEQ ID NO.: 
               
               
                 301-AS 
                   
                 50 
               
               
                   
               
               
                 CTNNB1 
                   TTTT ACCAGGTTAGTGAAACGCAGA 
                 SEQ ID NO.: 
               
               
                 302-AS 
                   
                 51 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TTTTGTGGGTGTAATAGTGAC 
                 SEQ ID NO.: 
               
               
                 321-S 
                   
                 52 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TTTGTGGGTGTAATAGTGACA 
                 SEQ ID NO.: 
               
               
                 322-S 
                   
                 53 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TTGTGGGTGTAATAGTGACAT 
                 SEQ ID NO.: 
               
               
                 323-S 
                   
                 54 
               
               
                   
               
               
                 CTNNB1 
                   TTTT TGTGGGTGTAATAGTGACATT 
                 SEQ ID NO.: 
               
               
                 324-S 
                   
                 55 
               
               
                   
               
               
                 CTNNB1 
                   TTTT GTGGGTGTAATAGTGACATTT 
                 SEQ ID NO.: 
               
               
                 325-S 
                   
                 56 
               
               
                   
               
               
                 CTNNB1_FWD 
                 TCCCACTGTACCTCTGTTATCCA 
                 SEQ ID NO.: 
               
               
                   
                   
                 57 
               
               
                   
               
               
                 CTNNB1_REV 
                 TGGTCCTCGTCATTTAGCAGTTT 
                 SEQ ID NO.: 
               
               
                   
                   
                 58 
               
               
                   
               
            
           
         
       
     
     Referring to  FIG.  4   , T7EI assay revealed significant improvement of the targeting efficiency by M537R and F870L mutations. First, M537R, F870L or the double-mutant (M537R/F870L) enabled efficient cleavage at all 15 sites with TTTT PAM, where 11 of 15 have no detectable cleavage by WT-Cpf1. For other sites with canonical TTTV PAM, these variants maintained or improved the targeting efficiency. The benefit is particularly significant at those low-activity sites, such as CTNNB1 111-s (3-fold improvement over WT). Among these variants, the double-mutant (M537R/F870) has the most consistent improvement of targeting efficiency across all tested sites, where the singly mutants exhibited more site-dependent variations, such as F870L at 323-S(no activity, same as WT). Overall, the described invention exhibits vastly superior on-target potency than the WT-Cpf1. 
     Example 5. High-Throughput Measurement of the DNA Cleavage Activity of AsCas12a Variants at TTTT PAM Site in  E. coli    
     The following Example demonstrates the robustness of our novel high-throughput screening strategy to directly measure the cleavage activity of thousands AsCas12a variants at TTTT PAM site in the bacterial-based activity assay ( FIG.  5   ).  FIG.  5 A-F  shows exemplary high-throughput phenotype measurement of AsCas12a point mutations by deep-scanning mutagenesis. A library encompassing every possible single point mutation of AsCas12a in the targeted region (499-640 and 840-913) was generated in the context of WT-AsCas12a or M537R/F870L-AsCas12a. The relative survival rate of each variant over the reference protein in an  E. coli -based activity assay was determined by deep-sequencing. The phenotype of individual point mutations was measured under multiple selection stringencies in the context of M537R/F870L (condition 1 and 2), and a third condition in the WT-AsCas12a background (condition 3). As shown in  FIG.  5 A-C , the phenotype scores (i.e. natural logarithm of relative survival rate) of variants are positively correlated under different conditions (ρ˜0.7), demonstrating the consistency and reproducibility of this approach. As the positive control, only the M537R and F870L/I, but not any other substitutions at these positions, survived more than the WT-AsCas12a ( FIG.  5 D ). Conversely, mutating R537 or L870 on the M537R/F870L-AsCas12a ubiquitously reduced the survival rate ( FIG.  5 E ). These results demonstrated that the phenotype score measured by the bacterial screening reflects the DNA cleavage activity of previously characterized AsCas12a variants at TTTT PAM. 
     To further validate the result of our bacterial screen, we studied four point mutations of AsCas12a with greater survival rate than the reference under all three conditions (L505K, S510L, P569D and P599G,  FIG.  5 F ), Of note, P599G has been shown to enhance the cleavage activity of AsCas12a at TTCC PAM. The other three point mutations have not been characterized by any published studies so far. We therefore measured the survival rate of  E. coli  cells transformed with plasmids expressing individual AsCas12a variant under selection. Compared to WT-AsCas12a, all selected point mutations increased the survival rate when targeting a TTTT-PAM site ( FIG.  6   ). Unexpectedly, the benefits of these point mutations held true even in the context of M537R/F870L-AsCasl2a, where the survival rate was further elevated ( FIG.  7   ). Collectively, these results demonstrated that our high-throughput screening can accurately predict the phenotype of uncharacterized AsCas12a variants. 
     The phenotype scores of 3,194 AsCas12a variants with single point mutation covered by the screening with sufficient sequencing count are listed in Table 3. Overall, ˜60% exhibited some benefits (i.e. phenotype score&gt;0) in one of the three condition. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Summary of selected variants in different background conditions. 1   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                 Consistent 
               
               
                   
                 Enrich. 
                 Stand. 
                 Enrich. 
                 Stand. 
                 Enrich. 
                 Stand. 
                 Any positive 
                 positive 
               
               
                 Mutant 
                 Score (1) 
                 Error (1) 
                 Score (2) 
                 Error (2) 
                 Score (3) 
                 Error (3) 
                 enrichment? 
                 enrichment? 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 R499C 
                 0.14 
                 0.08 
                 0.60 
                 0.07 
                 0.06 
                 0.10 
                 Yes 
                 Yes 
               
               
                 R499L 
                 0.08 
                 0.05 
                 0.05 
                 0.06 
                 0.09 
                 0.15 
                 Yes 
                 Yes 
               
               
                 R499K 
                 0.54 
                 0.06 
                 0.23 
                 0.06 
                 0.38 
                 0.10 
                 Yes 
                 Yes 
               
               
                 R499A 
                 −0.29 
                 0.05 
                 0.27 
                 0.04 
                 0.22 
                 0.07 
                 Yes 
                 No 
               
               
                 R499N 
                 0.39 
                 0.11 
                 −0.49 
                 0.15 
                 −0.13 
                 0.29 
                 Yes 
                 No 
               
               
                 R499D 
                 0.03 
                 0.09 
                 −1.01 
                 0.12 
                 −0.51 
                 0.44 
                 Yes 
                 No 
               
               
                 R499Q 
                 −0.10 
                 0.08 
                 0.42 
                 0.07 
                 0.19 
                 0.20 
                 Yes 
                 No 
               
               
                 R499E 
                 −0.23 
                 0.06 
                 0.50 
                 0.05 
                 −0.10 
                 0.10 
                 Yes 
                 No 
               
               
                 R499G 
                 −0.11 
                 0.03 
                 0.12 
                 0.03 
                 0.14 
                 0.06 
                 Yes 
                 No 
               
               
                 R499H 
                 −0.45 
                 0.11 
                 0.50 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R499I 
                 −0.14 
                 0.10 
                 0.09 
                 0.09 
                 −0.18 
                 0.13 
                 Yes 
                 No 
               
               
                 R499M 
                 −0.44 
                 0.09 
                 0.50 
                 0.07 
                 0.27 
                 0.21 
                 Yes 
                 No 
               
               
                 R499F 
                 0.01 
                 0.15 
                 −0.31 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R499P 
                 −0.56 
                 0.08 
                 −0.06 
                 0.07 
                 −0.70 
                 0.26 
                 No 
                 No 
               
               
                 R499S 
                 −0.14 
                 0.05 
                 0.02 
                 0.05 
                 −0.04 
                 0.06 
                 Yes 
                 No 
               
               
                 R499* 
                 −0.76 
                 0.10 
                 −0.61 
                 0.10 
                 −1.06 
                 0.18 
                 No 
                 No 
               
               
                 R499T 
                 −0.01 
                 0.07 
                 0.56 
                 0.06 
                 0.23 
                 0.16 
                 Yes 
                 No 
               
               
                 R499W 
                 −0.27 
                 0.05 
                 0.11 
                 0.05 
                 −0.53 
                 0.11 
                 Yes 
                 No 
               
               
                 R499V 
                 0.09 
                 0.05 
                 0.09 
                 0.05 
                 −0.10 
                 0.14 
                 Yes 
                 No 
               
               
                 L500M 
                 0.01 
                 0.05 
                 0.30 
                 0.05 
                 0.28 
                 0.12 
                 Yes 
                 Yes 
               
               
                 L500A 
                 −0.27 
                 0.04 
                 0.21 
                 0.03 
                 −0.15 
                 0.07 
                 Yes 
                 No 
               
               
                 L500R 
                 −0.35 
                 0.03 
                 −0.40 
                 0.03 
                 −0.47 
                 0.05 
                 No 
                 No 
               
               
                 L500N 
                 −1.11 
                 0.14 
                 −0.60 
                 0.12 
                 −0.50 
                 0.16 
                 No 
                 No 
               
               
                 L500D 
                 −1.03 
                 0.08 
                 −1.98 
                 0.13 
                 −1.26 
                 0.19 
                 No 
                 No 
               
               
                 L500C 
                 −0.19 
                 0.05 
                 0.26 
                 0.05 
                 0.00 
                 0.10 
                 Yes 
                 No 
               
               
                 L500Q 
                 −0.67 
                 0.06 
                 −0.63 
                 0.06 
                 −0.13 
                 0.07 
                 No 
                 No 
               
               
                 L500E 
                 −1.00 
                 0.06 
                 −1.22 
                 0.07 
                 −1.29 
                 0.07 
                 No 
                 No 
               
               
                 L500G 
                 −0.72 
                 0.03 
                 −0.79 
                 0.03 
                 −0.84 
                 0.03 
                 No 
                 No 
               
               
                 L500H 
                 −0.30 
                 0.09 
                 0.01 
                 0.08 
                 0.01 
                 0.22 
                 Yes 
                 No 
               
               
                 L500I 
                 −0.31 
                 0.09 
                 0.07 
                 0.08 
                 0.26 
                 0.15 
                 Yes 
                 No 
               
               
                 L500K 
                 −1.21 
                 0.09 
                 −0.32 
                 0.07 
                 −0.28 
                 0.07 
                 No 
                 No 
               
               
                 L500F 
                 −0.19 
                 0.08 
                 −0.33 
                 0.09 
                 0.09 
                 0.21 
                 Yes 
                 No 
               
               
                 L500P 
                 −0.79 
                 0.05 
                 −0.80 
                 0.05 
                 −0.91 
                 0.07 
                 No 
                 No 
               
               
                 L500S 
                 −0.84 
                 0.04 
                 −0.43 
                 0.04 
                 −0.37 
                 0.07 
                 No 
                 No 
               
               
                 L500* 
                 −1.39 
                 0.09 
                 −1.60 
                 0.11 
                 −1.66 
                 0.16 
                 No 
                 No 
               
               
                 L500T 
                 −0.19 
                 0.05 
                 −0.37 
                 0.06 
                 −0.17 
                 0.06 
                 No 
                 No 
               
               
                 L500W 
                 −0.25 
                 0.04 
                 −0.29 
                 0.04 
                 0.01 
                 0.11 
                 Yes 
                 No 
               
               
                 L500Y 
                 −0.01 
                 0.09 
                 0.04 
                 0.09 
                 0.05 
                 0.22 
                 Yes 
                 No 
               
               
                 L500V 
                 −0.13 
                 0.03 
                 0.11 
                 0.03 
                 −0.03 
                 0.06 
                 Yes 
                 No 
               
               
                 T501L 
                 0.18 
                 0.04 
                 0.32 
                 0.04 
                 0.12 
                 0.07 
                 Yes 
                 Yes 
               
               
                 T501M 
                 0.32 
                 0.07 
                 0.35 
                 0.07 
                 0.17 
                 0.29 
                 Yes 
                 Yes 
               
               
                 T501V 
                 0.22 
                 0.06 
                 0.29 
                 0.06 
                 0.13 
                 0.20 
                 Yes 
                 Yes 
               
               
                 T501A 
                 −0.06 
                 0.03 
                 −0.13 
                 0.03 
                 −0.07 
                 0.10 
                 No 
                 No 
               
               
                 T501R 
                 0.01 
                 0.03 
                 −0.16 
                 0.03 
                 0.54 
                 0.07 
                 Yes 
                 No 
               
               
                 T501N 
                 0.69 
                 0.14 
                 0.16 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T501D 
                 0.12 
                 0.12 
                 −0.12 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T501C 
                 0.52 
                 0.09 
                 −0.40 
                 0.11 
                 0.31 
                 0.26 
                 Yes 
                 No 
               
               
                 T501Q 
                 −0.19 
                 0.10 
                 −0.04 
                 0.10 
                 −0.24 
                 0.31 
                 No 
                 No 
               
               
                 T501E 
                 −0.39 
                 0.09 
                 0.05 
                 0.08 
                 −0.34 
                 0.26 
                 Yes 
                 No 
               
               
                 T501G 
                 0.12 
                 0.04 
                 0.44 
                 0.04 
                 −0.03 
                 0.09 
                 Yes 
                 No 
               
               
                 T501I 
                 0.13 
                 0.07 
                 0.05 
                 0.07 
                 −0.19 
                 0.11 
                 Yes 
                 No 
               
               
                 T501K 
                 −0.30 
                 0.09 
                 0.21 
                 0.08 
                 0.55 
                 0.24 
                 Yes 
                 No 
               
               
                 T501F 
                 0.08 
                 0.08 
                 −0.12 
                 0.08 
                 −0.12 
                 0.14 
                 Yes 
                 No 
               
               
                 T501P 
                 −0.29 
                 0.07 
                 0.14 
                 0.06 
                 −0.39 
                 0.13 
                 Yes 
                 No 
               
               
                 T501S 
                 0.06 
                 0.05 
                 0.14 
                 0.05 
                 −0.10 
                 0.09 
                 Yes 
                 No 
               
               
                 T501* 
                 −1.18 
                 0.12 
                 −0.58 
                 0.10 
                 −0.85 
                 0.21 
                 No 
                 No 
               
               
                 T501W 
                 −0.02 
                 0.07 
                 0.26 
                 0.06 
                 −0.30 
                 0.09 
                 Yes 
                 No 
               
               
                 T501Y 
                 −0.08 
                 0.12 
                 0.11 
                 0.12 
                 −0.29 
                 0.29 
                 Yes 
                 No 
               
               
                 G502R 
                 0.14 
                 0.05 
                 0.28 
                 0.05 
                 0.98 
                 0.07 
                 Yes 
                 Yes 
               
               
                 G502E 
                 0.42 
                 0.08 
                 0.17 
                 0.08 
                 0.19 
                 0.30 
                 Yes 
                 Yes 
               
               
                 G502L 
                 0.45 
                 0.07 
                 0.10 
                 0.07 
                 0.00 
                 0.11 
                 Yes 
                 Yes 
               
               
                 G502S 
                 0.08 
                 0.06 
                 0.23 
                 0.06 
                 0.16 
                 0.12 
                 Yes 
                 Yes 
               
               
                 G502W 
                 0.14 
                 0.07 
                 0.65 
                 0.06 
                 0.36 
                 0.14 
                 Yes 
                 Yes 
               
               
                 G502V 
                 0.21 
                 0.05 
                 0.21 
                 0.05 
                 0.13 
                 0.07 
                 Yes 
                 Yes 
               
               
                 G502A 
                 −0.05 
                 0.05 
                 −0.34 
                 0.05 
                 0.08 
                 0.07 
                 Yes 
                 No 
               
               
                 G502D 
                 −0.14 
                 0.08 
                 0.37 
                 0.07 
                 0.10 
                 0.15 
                 Yes 
                 No 
               
               
                 G502C 
                 −0.17 
                 0.08 
                 0.23 
                 0.08 
                 −0.04 
                 0.13 
                 Yes 
                 No 
               
               
                 G502Q 
                 0.78 
                 0.11 
                 0.02 
                 0.13 
                 −0.06 
                 0.55 
                 Yes 
                 No 
               
               
                 G502H 
                 0.61 
                 0.15 
                 0.01 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G502M 
                 −0.34 
                 0.13 
                 0.35 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G502F 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.08 
                 0.37 
                 Yes 
                 No 
               
               
                 G502P 
                 −0.41 
                 0.14 
                 0.01 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G502* 
                 −1.16 
                 0.15 
                 −0.82 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G502T 
                 0.69 
                 0.10 
                 −0.23 
                 0.13 
                 0.24 
                 0.35 
                 Yes 
                 No 
               
               
                 I503A 
                 −0.76 
                 0.09 
                 0.32 
                 0.07 
                 −0.16 
                 0.21 
                 Yes 
                 No 
               
               
                 I503R 
                 −0.86 
                 0.07 
                 −0.67 
                 0.07 
                 −0.51 
                 0.17 
                 No 
                 No 
               
               
                 I503N 
                 −0.03 
                 0.09 
                 −0.30 
                 0.10 
                 −0.26 
                 0.17 
                 No 
                 No 
               
               
                 I503D 
                 −0.50 
                 0.13 
                 −0.57 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I503C 
                 −0.24 
                 0.11 
                 0.84 
                 0.09 
                 0.00 
                 0.33 
                 Yes 
                 No 
               
               
                 I503E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.71 
                 0.36 
                 Yes 
                 No 
               
               
                 I503G 
                 −0.69 
                 0.06 
                 −0.30 
                 0.05 
                 −0.53 
                 0.15 
                 No 
                 No 
               
               
                 I503L 
                 0.13 
                 0.06 
                 −0.46 
                 0.07 
                 −0.31 
                 0.15 
                 Yes 
                 No 
               
               
                 I503K 
                 0.03 
                 0.12 
                 −0.51 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I503M 
                 −0.08 
                 0.10 
                 −0.17 
                 0.10 
                 −0.13 
                 0.27 
                 No 
                 No 
               
               
                 I503F 
                 −0.17 
                 0.09 
                 −0.17 
                 0.09 
                 −0.25 
                 0.19 
                 No 
                 No 
               
               
                 I503S 
                 −0.45 
                 0.07 
                 −0.27 
                 0.07 
                 −0.23 
                 0.19 
                 No 
                 No 
               
               
                 I503T 
                 −0.23 
                 0.08 
                 0.33 
                 0.07 
                 0.20 
                 0.14 
                 Yes 
                 No 
               
               
                 I503W 
                 −1.21 
                 0.11 
                 −0.88 
                 0.10 
                 −0.61 
                 0.28 
                 No 
                 No 
               
               
                 I503V 
                 −0.09 
                 0.05 
                 0.34 
                 0.04 
                 −0.03 
                 0.09 
                 Yes 
                 No 
               
               
                 K504A 
                 −0.15 
                 0.07 
                 −0.33 
                 0.07 
                 −0.30 
                 0.20 
                 No 
                 No 
               
               
                 K504R 
                 −0.05 
                 0.03 
                 0.04 
                 0.03 
                 −0.08 
                 0.06 
                 Yes 
                 No 
               
               
                 K504N 
                 0.01 
                 0.03 
                 −0.54 
                 0.04 
                 −0.50 
                 0.04 
                 Yes 
                 No 
               
               
                 K504C 
                 −0.46 
                 0.13 
                 0.02 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K504Q 
                 −0.16 
                 0.05 
                 −0.25 
                 0.05 
                 −0.22 
                 0.07 
                 No 
                 No 
               
               
                 K504E 
                 −0.03 
                 0.05 
                 −0.32 
                 0.06 
                 −0.65 
                 0.11 
                 No 
                 No 
               
               
                 K504G 
                 −0.84 
                 0.05 
                 −0.46 
                 0.05 
                 −0.52 
                 0.15 
                 No 
                 No 
               
               
                 K504H 
                 −0.59 
                 0.13 
                 −0.01 
                 0.11 
                 −0.51 
                 0.16 
                 No 
                 No 
               
               
                 K504I 
                 −0.07 
                 0.08 
                 0.12 
                 0.07 
                 −0.31 
                 0.14 
                 Yes 
                 No 
               
               
                 K504L 
                 −0.39 
                 0.05 
                 −0.05 
                 0.05 
                 −0.10 
                 0.14 
                 No 
                 No 
               
               
                 K504M 
                 −0.32 
                 0.08 
                 −0.06 
                 0.08 
                 −0.06 
                 0.10 
                 No 
                 No 
               
               
                 K504F 
                 −0.71 
                 0.14 
                 −0.24 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K504S 
                 −0.50 
                 0.08 
                 −0.45 
                 0.08 
                 −0.19 
                 0.23 
                 No 
                 No 
               
               
                 K504* 
                 −0.43 
                 0.09 
                 −0.59 
                 0.10 
                 −0.76 
                 0.15 
                 No 
                 No 
               
               
                 K504T 
                 −0.22 
                 0.08 
                 0.08 
                 0.07 
                 −0.15 
                 0.14 
                 Yes 
                 No 
               
               
                 K504W 
                 −0.48 
                 0.08 
                 0.09 
                 0.07 
                 −0.53 
                 0.24 
                 Yes 
                 No 
               
               
                 K504V 
                 −0.48 
                 0.05 
                 −0.27 
                 0.05 
                 −0.36 
                 0.12 
                 No 
                 No 
               
               
                 L505A 
                 0.61 
                 0.05 
                 0.50 
                 0.05 
                 0.47 
                 0.13 
                 Yes 
                 Yes 
               
               
                 L505R 
                 0.40 
                 0.03 
                 0.56 
                 0.03 
                 0.81 
                 0.05 
                 Yes 
                 Yes 
               
               
                 L505Q 
                 0.30 
                 0.07 
                 0.82 
                 0.07 
                 0.16 
                 0.11 
                 Yes 
                 Yes 
               
               
                 L505E 
                 0.18 
                 0.06 
                 0.03 
                 0.07 
                 0.14 
                 0.21 
                 Yes 
                 Yes 
               
               
                 L505G 
                 0.18 
                 0.03 
                 0.72 
                 0.03 
                 0.40 
                 0.05 
                 Yes 
                 Yes 
               
               
                 L505H 
                 0.33 
                 0.11 
                 0.83 
                 0.10 
                 0.34 
                 0.32 
                 Yes 
                 Yes 
               
               
                 L505K 
                 0.02 
                 0.10 
                 1.00 
                 0.08 
                 1.00 
                 0.13 
                 Yes 
                 Yes 
               
               
                 L505S 
                 0.13 
                 0.06 
                 0.32 
                 0.06 
                 0.60 
                 0.07 
                 Yes 
                 Yes 
               
               
                 L505N 
                 −0.53 
                 0.17 
                 0.27 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L505D 
                 −0.28 
                 0.11 
                 0.59 
                 0.10 
                 0.10 
                 0.49 
                 Yes 
                 No 
               
               
                 L505C 
                 0.26 
                 0.07 
                 −0.14 
                 0.08 
                 0.47 
                 0.27 
                 Yes 
                 No 
               
               
                 L505M 
                 −0.05 
                 0.09 
                 −0.06 
                 0.09 
                 −0.18 
                 0.18 
                 No 
                 No 
               
               
                 L505F 
                 −0.97 
                 0.15 
                 0.28 
                 0.11 
                 −0.33 
                 0.41 
                 Yes 
                 No 
               
               
                 L505P 
                 −0.55 
                 0.07 
                 −0.09 
                 0.06 
                 −0.09 
                 0.11 
                 No 
                 No 
               
               
                 L505T 
                 −0.23 
                 0.09 
                 0.44 
                 0.08 
                 0.59 
                 0.17 
                 Yes 
                 No 
               
               
                 L505W 
                 −0.03 
                 0.06 
                 0.28 
                 0.05 
                 −0.19 
                 0.17 
                 Yes 
                 No 
               
               
                 L505V 
                 −0.03 
                 0.04 
                 0.15 
                 0.04 
                 0.45 
                 0.11 
                 Yes 
                 No 
               
               
                 E506A 
                 0.33 
                 0.03 
                 0.47 
                 0.03 
                 0.70 
                 0.05 
                 Yes 
                 Yes 
               
               
                 E506R 
                 0.46 
                 0.03 
                 0.81 
                 0.03 
                 1.20 
                 0.04 
                 Yes 
                 Yes 
               
               
                 E506N 
                 0.24 
                 0.09 
                 0.53 
                 0.09 
                 0.50 
                 0.29 
                 Yes 
                 Yes 
               
               
                 E506C 
                 0.20 
                 0.06 
                 0.29 
                 0.06 
                 0.49 
                 0.19 
                 Yes 
                 Yes 
               
               
                 E506Q 
                 0.09 
                 0.07 
                 0.74 
                 0.06 
                 0.33 
                 0.15 
                 Yes 
                 Yes 
               
               
                 E506G 
                 0.24 
                 0.02 
                 0.39 
                 0.02 
                 0.53 
                 0.03 
                 Yes 
                 Yes 
               
               
                 E506H 
                 0.35 
                 0.09 
                 0.10 
                 0.10 
                 0.98 
                 0.31 
                 Yes 
                 Yes 
               
               
                 E506I 
                 0.47 
                 0.09 
                 0.45 
                 0.09 
                 0.69 
                 0.13 
                 Yes 
                 Yes 
               
               
                 E506L 
                 0.30 
                 0.04 
                 0.61 
                 0.04 
                 0.56 
                 0.07 
                 Yes 
                 Yes 
               
               
                 E506K 
                 0.18 
                 0.06 
                 0.59 
                 0.05 
                 1.08 
                 0.08 
                 Yes 
                 Yes 
               
               
                 E506M 
                 0.53 
                 0.06 
                 0.28 
                 0.07 
                 0.47 
                 0.17 
                 Yes 
                 Yes 
               
               
                 E506S 
                 0.01 
                 0.05 
                 0.47 
                 0.04 
                 0.50 
                 0.06 
                 Yes 
                 Yes 
               
               
                 E506T 
                 0.39 
                 0.06 
                 0.12 
                 0.07 
                 0.90 
                 0.23 
                 Yes 
                 Yes 
               
               
                 E506Y 
                 0.16 
                 0.09 
                 0.29 
                 0.09 
                 0.43 
                 0.25 
                 Yes 
                 Yes 
               
               
                 E506V 
                 0.45 
                 0.03 
                 0.51 
                 0.03 
                 0.75 
                 0.05 
                 Yes 
                 Yes 
               
               
                 E506D 
                 0.19 
                 0.04 
                 −0.30 
                 0.05 
                 −0.08 
                 0.08 
                 Yes 
                 No 
               
               
                 E506F 
                 −0.21 
                 0.10 
                 0.47 
                 0.08 
                 0.20 
                 0.25 
                 Yes 
                 No 
               
               
                 E506P 
                 −0.07 
                 0.08 
                 0.37 
                 0.07 
                 0.52 
                 0.26 
                 Yes 
                 No 
               
               
                 E506* 
                 −0.79 
                 0.08 
                 −0.79 
                 0.08 
                 −1.11 
                 0.07 
                 No 
                 No 
               
               
                 E506W 
                 0.43 
                 0.04 
                 0.10 
                 0.04 
                 −0.07 
                 0.05 
                 Yes 
                 No 
               
               
                 M507A 
                 −0.47 
                 0.06 
                 −0.34 
                 0.06 
                 −0.32 
                 0.19 
                 No 
                 No 
               
               
                 M507R 
                 −0.42 
                 0.02 
                 −0.58 
                 0.03 
                 −0.64 
                 0.04 
                 No 
                 No 
               
               
                 M507C 
                 −0.41 
                 0.09 
                 −0.31 
                 0.09 
                 0.15 
                 0.28 
                 Yes 
                 No 
               
               
                 M507Q 
                 −0.68 
                 0.07 
                 −0.56 
                 0.07 
                 −0.44 
                 0.17 
                 No 
                 No 
               
               
                 M507E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.23 
                 0.19 
                 Yes 
                 No 
               
               
                 M507G 
                 −0.98 
                 0.05 
                 −0.71 
                 0.05 
                 −1.24 
                 0.12 
                 No 
                 No 
               
               
                 M507H 
                 −0.65 
                 0.12 
                 0.68 
                 0.09 
                 −0.86 
                 0.28 
                 Yes 
                 No 
               
               
                 M507I 
                 −0.06 
                 0.04 
                 −0.12 
                 0.04 
                 0.01 
                 0.07 
                 Yes 
                 No 
               
               
                 M507L 
                 −0.20 
                 0.03 
                 −0.35 
                 0.03 
                 −0.16 
                 0.03 
                 No 
                 No 
               
               
                 M507K 
                 −1.42 
                 0.13 
                 −0.06 
                 0.09 
                 −1.00 
                 0.19 
                 No 
                 No 
               
               
                 M507F 
                 0.05 
                 0.09 
                 −0.78 
                 0.12 
                 −0.05 
                 0.36 
                 Yes 
                 No 
               
               
                 M507P 
                 −2.08 
                 0.12 
                 −2.19 
                 0.13 
                 −1.58 
                 0.18 
                 No 
                 No 
               
               
                 M507S 
                 −1.03 
                 0.09 
                 −0.34 
                 0.07 
                 −0.46 
                 0.18 
                 No 
                 No 
               
               
                 M507* 
                 −1.68 
                 0.15 
                 −0.72 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M507T 
                 −0.11 
                 0.06 
                 −0.30 
                 0.07 
                 −0.03 
                 0.13 
                 No 
                 No 
               
               
                 M507W 
                 −0.94 
                 0.08 
                 −0.59 
                 0.07 
                 −0.82 
                 0.18 
                 No 
                 No 
               
               
                 M507V 
                 −0.17 
                 0.03 
                 0.06 
                 0.03 
                 −0.28 
                 0.06 
                 Yes 
                 No 
               
               
                 E508A 
                 0.36 
                 0.03 
                 0.20 
                 0.03 
                 0.18 
                 0.06 
                 Yes 
                 Yes 
               
               
                 E508R 
                 0.54 
                 0.03 
                 0.80 
                 0.03 
                 0.82 
                 0.06 
                 Yes 
                 Yes 
               
               
                 E508Q 
                 0.25 
                 0.06 
                 0.11 
                 0.07 
                 0.51 
                 0.13 
                 Yes 
                 Yes 
               
               
                 E508G 
                 0.16 
                 0.02 
                 0.17 
                 0.02 
                 0.22 
                 0.04 
                 Yes 
                 Yes 
               
               
                 E508L 
                 0.03 
                 0.04 
                 0.10 
                 0.04 
                 0.26 
                 0.11 
                 Yes 
                 Yes 
               
               
                 E508K 
                 0.20 
                 0.06 
                 0.49 
                 0.06 
                 0.66 
                 0.08 
                 Yes 
                 Yes 
               
               
                 E508M 
                 0.25 
                 0.07 
                 0.57 
                 0.06 
                 0.54 
                 0.11 
                 Yes 
                 Yes 
               
               
                 E508F 
                 0.27 
                 0.08 
                 0.19 
                 0.08 
                 0.39 
                 0.29 
                 Yes 
                 Yes 
               
               
                 E508S 
                 0.31 
                 0.05 
                 0.62 
                 0.04 
                 0.34 
                 0.06 
                 Yes 
                 Yes 
               
               
                 E508T 
                 0.19 
                 0.06 
                 0.73 
                 0.06 
                 0.55 
                 0.10 
                 Yes 
                 Yes 
               
               
                 E508Y 
                 0.35 
                 0.09 
                 0.19 
                 0.10 
                 0.21 
                 0.27 
                 Yes 
                 Yes 
               
               
                 E508V 
                 0.16 
                 0.03 
                 0.22 
                 0.03 
                 0.34 
                 0.05 
                 Yes 
                 Yes 
               
               
                 E508N 
                 −0.08 
                 0.11 
                 −0.10 
                 0.11 
                 0.55 
                 0.20 
                 Yes 
                 No 
               
               
                 E508D 
                 0.09 
                 0.04 
                 −0.15 
                 0.04 
                 −0.16 
                 0.06 
                 Yes 
                 No 
               
               
                 E508C 
                 −0.15 
                 0.08 
                 0.18 
                 0.07 
                 0.02 
                 0.24 
                 Yes 
                 No 
               
               
                 E508H 
                 −0.25 
                 0.11 
                 0.57 
                 0.09 
                 0.65 
                 0.24 
                 Yes 
                 No 
               
               
                 E508I 
                 0.29 
                 0.09 
                 −0.12 
                 0.10 
                 0.54 
                 0.15 
                 Yes 
                 No 
               
               
                 E508P 
                 −0.52 
                 0.08 
                 −0.67 
                 0.08 
                 −0.63 
                 0.20 
                 No 
                 No 
               
               
                 E508* 
                 −0.63 
                 0.06 
                 −0.82 
                 0.07 
                 −0.79 
                 0.09 
                 No 
                 No 
               
               
                 E508W 
                 −0.29 
                 0.05 
                 0.45 
                 0.05 
                 0.07 
                 0.09 
                 Yes 
                 No 
               
               
                 P509R 
                 0.23 
                 0.03 
                 0.27 
                 0.03 
                 1.04 
                 0.05 
                 Yes 
                 Yes 
               
               
                 P509K 
                 0.01 
                 0.07 
                 0.12 
                 0.07 
                 1.29 
                 0.13 
                 Yes 
                 Yes 
               
               
                 P509M 
                 0.34 
                 0.07 
                 0.34 
                 0.07 
                 0.10 
                 0.22 
                 Yes 
                 Yes 
               
               
                 P509S 
                 0.10 
                 0.04 
                 0.14 
                 0.04 
                 0.14 
                 0.10 
                 Yes 
                 Yes 
               
               
                 P509W 
                 0.04 
                 0.05 
                 0.33 
                 0.05 
                 0.61 
                 0.18 
                 Yes 
                 Yes 
               
               
                 P509Y 
                 0.18 
                 0.09 
                 0.20 
                 0.09 
                 0.53 
                 0.30 
                 Yes 
                 Yes 
               
               
                 P509A 
                 0.45 
                 0.04 
                 −0.19 
                 0.04 
                 −0.04 
                 0.05 
                 Yes 
                 No 
               
               
                 P509N 
                 0.18 
                 0.09 
                 −0.33 
                 0.11 
                 0.63 
                 0.29 
                 Yes 
                 No 
               
               
                 P509D 
                 −0.12 
                 0.08 
                 −0.12 
                 0.08 
                 −0.01 
                 0.21 
                 No 
                 No 
               
               
                 P509C 
                 0.00 
                 0.06 
                 −0.37 
                 0.07 
                 0.05 
                 0.20 
                 Yes 
                 No 
               
               
                 P509Q 
                 0.08 
                 0.05 
                 −0.10 
                 0.06 
                 0.36 
                 0.08 
                 Yes 
                 No 
               
               
                 P509E 
                 −0.27 
                 0.06 
                 0.33 
                 0.05 
                 0.38 
                 0.17 
                 Yes 
                 No 
               
               
                 P509G 
                 −0.06 
                 0.03 
                 0.19 
                 0.03 
                 0.00 
                 0.05 
                 Yes 
                 No 
               
               
                 P509H 
                 0.09 
                 0.03 
                 −0.31 
                 0.03 
                 −0.19 
                 0.05 
                 Yes 
                 No 
               
               
                 P509I 
                 −0.10 
                 0.09 
                 −0.34 
                 0.10 
                 −0.56 
                 0.28 
                 No 
                 No 
               
               
                 P509L 
                 0.11 
                 0.04 
                 0.17 
                 0.04 
                 −0.17 
                 0.05 
                 Yes 
                 No 
               
               
                 P509F 
                 −0.12 
                 0.09 
                 0.24 
                 0.08 
                 0.52 
                 0.11 
                 Yes 
                 No 
               
               
                 P509* 
                 −2.22 
                 0.15 
                 −0.93 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P509T 
                 0.10 
                 0.06 
                 0.58 
                 0.05 
                 −0.04 
                 0.11 
                 Yes 
                 No 
               
               
                 P509V 
                 0.09 
                 0.04 
                 0.07 
                 0.04 
                 −0.45 
                 0.08 
                 Yes 
                 No 
               
               
                 S510G 
                 0.18 
                 0.03 
                 0.49 
                 0.03 
                 0.21 
                 0.06 
                 Yes 
                 Yes 
               
               
                 S510L 
                 0.57 
                 0.06 
                 0.72 
                 0.06 
                 0.74 
                 0.09 
                 Yes 
                 Yes 
               
               
                 S510A 
                 0.29 
                 0.06 
                 −0.25 
                 0.07 
                 0.04 
                 0.22 
                 Yes 
                 No 
               
               
                 S510R 
                 −0.38 
                 0.03 
                 −0.43 
                 0.03 
                 −0.53 
                 0.04 
                 No 
                 No 
               
               
                 S510N 
                 −0.36 
                 0.09 
                 −0.11 
                 0.09 
                 0.06 
                 0.17 
                 Yes 
                 No 
               
               
                 S510D 
                 −1.40 
                 0.15 
                 −1.36 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S510C 
                 −0.14 
                 0.06 
                 0.03 
                 0.06 
                 0.28 
                 0.14 
                 Yes 
                 No 
               
               
                 S510E 
                 −0.71 
                 0.09 
                 −1.10 
                 0.11 
                 −1.07 
                 0.25 
                 No 
                 No 
               
               
                 S510I 
                 0.02 
                 0.05 
                 −0.39 
                 0.06 
                 −0.76 
                 0.03 
                 Yes 
                 No 
               
               
                 S510M 
                 −1.15 
                 0.14 
                 −0.15 
                 0.10 
                 0.36 
                 0.23 
                 Yes 
                 No 
               
               
                 S510F 
                 −0.15 
                 0.12 
                 0.48 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S510* 
                 −1.11 
                 0.13 
                 −1.36 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S510T 
                 0.18 
                 0.08 
                 0.64 
                 0.08 
                 −0.17 
                 0.16 
                 Yes 
                 No 
               
               
                 S510W 
                 −0.06 
                 0.06 
                 −0.94 
                 0.08 
                 −0.37 
                 0.17 
                 No 
                 No 
               
               
                 S510V 
                 −0.05 
                 0.05 
                 0.44 
                 0.05 
                 0.44 
                 0.18 
                 Yes 
                 No 
               
               
                 L511A 
                 0.07 
                 0.10 
                 −0.06 
                 0.11 
                 −0.31 
                 0.15 
                 Yes 
                 No 
               
               
                 L511R 
                 0.00 
                 0.03 
                 −0.21 
                 0.04 
                 0.09 
                 0.06 
                 Yes 
                 No 
               
               
                 L511Q 
                 −0.72 
                 0.15 
                 0.45 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L511E 
                 −0.31 
                 0.12 
                 −0.25 
                 0.13 
                 −0.81 
                 0.34 
                 No 
                 No 
               
               
                 L511G 
                 −0.42 
                 0.07 
                 0.08 
                 0.06 
                 −0.02 
                 0.27 
                 Yes 
                 No 
               
               
                 L511K 
                 0.26 
                 0.13 
                 0.44 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L511M 
                 −0.67 
                 0.11 
                 0.33 
                 0.08 
                 0.25 
                 0.20 
                 Yes 
                 No 
               
               
                 L511P 
                 0.04 
                 0.08 
                 0.00 
                 0.09 
                 0.26 
                 0.13 
                 Yes 
                 No 
               
               
                 L511S 
                 −0.12 
                 0.12 
                 −0.37 
                 0.13 
                 0.02 
                 0.33 
                 Yes 
                 No 
               
               
                 L511W 
                 0.61 
                 0.08 
                 0.02 
                 0.09 
                 −0.40 
                 0.38 
                 Yes 
                 No 
               
               
                 L511V 
                 −0.26 
                 0.06 
                 0.38 
                 0.06 
                 −0.02 
                 0.16 
                 Yes 
                 No 
               
               
                 S512R 
                 0.07 
                 0.07 
                 0.34 
                 0.07 
                 0.07 
                 0.19 
                 Yes 
                 Yes 
               
               
                 S512A 
                 0.11 
                 0.05 
                 −0.15 
                 0.06 
                 −0.16 
                 0.06 
                 Yes 
                 No 
               
               
                 S512N 
                 −0.12 
                 0.19 
                 0.58 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S512D 
                 −0.14 
                 0.12 
                 −0.33 
                 0.13 
                 0.47 
                 0.39 
                 Yes 
                 No 
               
               
                 S512C 
                 0.06 
                 0.08 
                 0.61 
                 0.08 
                 −0.18 
                 0.19 
                 Yes 
                 No 
               
               
                 S512E 
                 0.44 
                 0.10 
                 −0.11 
                 0.12 
                 0.21 
                 0.36 
                 Yes 
                 No 
               
               
                 S512G 
                 −0.15 
                 0.05 
                 −0.15 
                 0.05 
                 0.10 
                 0.12 
                 Yes 
                 No 
               
               
                 S512L 
                 −0.16 
                 0.10 
                 0.53 
                 0.09 
                 −0.21 
                 0.20 
                 Yes 
                 No 
               
               
                 S512K 
                 0.65 
                 0.15 
                 0.57 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S512M 
                 0.28 
                 0.14 
                 0.24 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S512F 
                 −0.28 
                 0.08 
                 −0.16 
                 0.08 
                 −0.32 
                 0.13 
                 No 
                 No 
               
               
                 S512P 
                 −0.22 
                 0.08 
                 −0.09 
                 0.08 
                 −0.16 
                 0.13 
                 No 
                 No 
               
               
                 S512T 
                 −0.17 
                 0.09 
                 0.05 
                 0.08 
                 −0.07 
                 0.15 
                 Yes 
                 No 
               
               
                 S512W 
                 −0.13 
                 0.10 
                 0.13 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S512Y 
                 −0.26 
                 0.13 
                 −0.68 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S512V 
                 −0.38 
                 0.08 
                 −0.54 
                 0.09 
                 −0.64 
                 0.19 
                 No 
                 No 
               
               
                 F513L 
                 0.53 
                 0.04 
                 0.63 
                 0.04 
                 0.41 
                 0.07 
                 Yes 
                 Yes 
               
               
                 F513W 
                 0.04 
                 0.06 
                 0.35 
                 0.06 
                 0.28 
                 0.13 
                 Yes 
                 Yes 
               
               
                 F513A 
                 −1.58 
                 0.11 
                 0.20 
                 0.06 
                 −0.49 
                 0.25 
                 Yes 
                 No 
               
               
                 F513R 
                 −1.56 
                 0.09 
                 −1.47 
                 0.09 
                 −0.89 
                 0.06 
                 No 
                 No 
               
               
                 F513D 
                 −1.02 
                 0.15 
                 0.12 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F513C 
                 −0.83 
                 0.10 
                 −0.27 
                 0.09 
                 −0.27 
                 0.14 
                 No 
                 No 
               
               
                 F513Q 
                 0.00 
                 0.13 
                 0.58 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F513E 
                 −0.37 
                 0.09 
                 0.33 
                 0.08 
                 −0.38 
                 0.38 
                 Yes 
                 No 
               
               
                 F513G 
                 −1.33 
                 0.06 
                 −0.80 
                 0.05 
                 −1.00 
                 0.13 
                 No 
                 No 
               
               
                 F513I 
                 0.78 
                 0.10 
                 0.21 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F513M 
                 −0.36 
                 0.12 
                 0.73 
                 0.10 
                 0.49 
                 0.23 
                 Yes 
                 No 
               
               
                 F513S 
                 −0.59 
                 0.07 
                 −0.47 
                 0.07 
                 −0.61 
                 0.10 
                 No 
                 No 
               
               
                 F513T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.35 
                 0.19 
                 Yes 
                 No 
               
               
                 F513Y 
                 −0.10 
                 0.10 
                 0.26 
                 0.09 
                 0.44 
                 0.12 
                 Yes 
                 No 
               
               
                 F513V 
                 −0.53 
                 0.06 
                 −0.27 
                 0.06 
                 0.06 
                 0.19 
                 Yes 
                 No 
               
               
                 Y514A 
                 −0.28 
                 0.05 
                 −0.43 
                 0.05 
                 −0.73 
                 0.13 
                 No 
                 No 
               
               
                 Y514R 
                 −0.23 
                 0.04 
                 −0.47 
                 0.05 
                 −0.86 
                 0.14 
                 No 
                 No 
               
               
                 Y514N 
                 −0.17 
                 0.09 
                 0.07 
                 0.08 
                 −0.53 
                 0.17 
                 Yes 
                 No 
               
               
                 Y514D 
                 −1.11 
                 0.10 
                 −1.20 
                 0.11 
                 −1.22 
                 0.16 
                 No 
                 No 
               
               
                 Y514C 
                 −0.39 
                 0.05 
                 −0.35 
                 0.05 
                 −0.55 
                 0.09 
                 No 
                 No 
               
               
                 Y514Q 
                 −1.35 
                 0.13 
                 −0.62 
                 0.10 
                 −1.01 
                 0.29 
                 No 
                 No 
               
               
                 Y514E 
                 −1.08 
                 0.08 
                 −0.93 
                 0.08 
                 −1.50 
                 0.19 
                 No 
                 No 
               
               
                 Y514G 
                 −0.76 
                 0.04 
                 −0.49 
                 0.04 
                 −1.06 
                 0.11 
                 No 
                 No 
               
               
                 Y514H 
                 0.39 
                 0.06 
                 0.29 
                 0.06 
                 −0.31 
                 0.12 
                 Yes 
                 No 
               
               
                 Y514I 
                 −0.14 
                 0.09 
                 −0.84 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y514L 
                 −0.37 
                 0.05 
                 −0.57 
                 0.05 
                 −0.73 
                 0.10 
                 No 
                 No 
               
               
                 Y514K 
                 −0.52 
                 0.09 
                 −1.28 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y514M 
                 −0.50 
                 0.07 
                 −0.38 
                 0.07 
                 −0.59 
                 0.19 
                 No 
                 No 
               
               
                 Y514F 
                 −0.29 
                 0.07 
                 0.14 
                 0.06 
                 −0.35 
                 0.11 
                 Yes 
                 No 
               
               
                 Y514S 
                 −0.33 
                 0.05 
                 −0.32 
                 0.05 
                 −0.86 
                 0.11 
                 No 
                 No 
               
               
                 Y514* 
                 −0.91 
                 0.08 
                 −1.20 
                 0.10 
                 −1.18 
                 0.13 
                 No 
                 No 
               
               
                 Y514T 
                 −1.01 
                 0.09 
                 −1.31 
                 0.10 
                 −0.98 
                 0.18 
                 No 
                 No 
               
               
                 Y514W 
                 0.17 
                 0.05 
                 0.46 
                 0.05 
                 −0.09 
                 0.23 
                 Yes 
                 No 
               
               
                 Y514V 
                 −0.45 
                 0.04 
                 −0.41 
                 0.04 
                 −0.92 
                 0.06 
                 No 
                 No 
               
               
                 N515A 
                 0.60 
                 0.06 
                 0.82 
                 0.06 
                 0.12 
                 0.11 
                 Yes 
                 Yes 
               
               
                 N515R 
                 0.63 
                 0.06 
                 0.82 
                 0.05 
                 0.19 
                 0.11 
                 Yes 
                 Yes 
               
               
                 N515I 
                 0.23 
                 0.07 
                 0.30 
                 0.07 
                 0.16 
                 0.14 
                 Yes 
                 Yes 
               
               
                 N515L 
                 0.33 
                 0.06 
                 0.53 
                 0.06 
                 0.07 
                 0.20 
                 Yes 
                 Yes 
               
               
                 N515T 
                 0.41 
                 0.08 
                 0.14 
                 0.08 
                 0.29 
                 0.16 
                 Yes 
                 Yes 
               
               
                 N515V 
                 0.50 
                 0.05 
                 0.49 
                 0.05 
                 0.45 
                 0.09 
                 Yes 
                 Yes 
               
               
                 N515D 
                 0.05 
                 0.06 
                 −0.17 
                 0.06 
                 −0.30 
                 0.10 
                 Yes 
                 No 
               
               
                 N515C 
                 0.59 
                 0.12 
                 0.62 
                 0.12 
                 −0.02 
                 0.30 
                 Yes 
                 No 
               
               
                 N515Q 
                 0.46 
                 0.11 
                 0.69 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N515E 
                 0.47 
                 0.07 
                 0.56 
                 0.07 
                 −0.14 
                 0.19 
                 Yes 
                 No 
               
               
                 N515G 
                 −0.10 
                 0.05 
                 0.37 
                 0.04 
                 −0.13 
                 0.07 
                 Yes 
                 No 
               
               
                 N515H 
                 0.09 
                 0.10 
                 −0.59 
                 0.13 
                 −0.25 
                 0.21 
                 Yes 
                 No 
               
               
                 N515K 
                 0.07 
                 0.08 
                 0.16 
                 0.08 
                 −0.13 
                 0.16 
                 Yes 
                 No 
               
               
                 N515M 
                 0.73 
                 0.09 
                 0.45 
                 0.10 
                 −0.01 
                 0.12 
                 Yes 
                 No 
               
               
                 N515F 
                 0.49 
                 0.12 
                 0.48 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N515P 
                 −1.10 
                 0.16 
                 −0.13 
                 0.12 
                 −0.32 
                 0.38 
                 No 
                 No 
               
               
                 N515S 
                 0.08 
                 0.05 
                 −0.15 
                 0.05 
                 0.19 
                 0.08 
                 Yes 
                 No 
               
               
                 N515W 
                 0.79 
                 0.08 
                 0.42 
                 0.09 
                 −0.60 
                 0.31 
                 Yes 
                 No 
               
               
                 N515Y 
                 −0.30 
                 0.12 
                 −0.55 
                 0.13 
                 0.03 
                 0.22 
                 Yes 
                 No 
               
               
                 K516R 
                 0.01 
                 0.03 
                 0.26 
                 0.03 
                 0.40 
                 0.06 
                 Yes 
                 Yes 
               
               
                 K516A 
                 0.25 
                 0.05 
                 0.13 
                 0.06 
                 −0.33 
                 0.21 
                 Yes 
                 No 
               
               
                 K516N 
                 0.37 
                 0.09 
                 0.01 
                 0.11 
                 −0.01 
                 0.16 
                 Yes 
                 No 
               
               
                 K516D 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.48 
                 0.31 
                 Yes 
                 No 
               
               
                 K516C 
                 −1.37 
                 0.13 
                 0.14 
                 0.08 
                 −0.36 
                 0.16 
                 Yes 
                 No 
               
               
                 K516Q 
                 0.08 
                 0.07 
                 −0.76 
                 0.10 
                 −0.08 
                 0.16 
                 Yes 
                 No 
               
               
                 K516E 
                 −0.23 
                 0.04 
                 −0.32 
                 0.05 
                 −0.33 
                 0.09 
                 No 
                 No 
               
               
                 K516G 
                 −0.34 
                 0.03 
                 −0.01 
                 0.03 
                 −0.34 
                 0.05 
                 No 
                 No 
               
               
                 K516I 
                 −0.29 
                 0.14 
                 −0.03 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K516L 
                 −0.29 
                 0.06 
                 −0.06 
                 0.06 
                 −0.56 
                 0.18 
                 No 
                 No 
               
               
                 K516M 
                 −0.29 
                 0.08 
                 −0.21 
                 0.08 
                 −0.31 
                 0.17 
                 No 
                 No 
               
               
                 K516P 
                 −0.37 
                 0.10 
                 −0.96 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K516S 
                 −0.34 
                 0.06 
                 0.23 
                 0.06 
                 −0.22 
                 0.21 
                 Yes 
                 No 
               
               
                 K516* 
                 −0.66 
                 0.09 
                 −0.86 
                 0.10 
                 −1.08 
                 0.19 
                 No 
                 No 
               
               
                 K516T 
                 −0.18 
                 0.04 
                 −0.43 
                 0.04 
                 −0.09 
                 0.06 
                 No 
                 No 
               
               
                 K516W 
                 −0.42 
                 0.06 
                 −0.55 
                 0.07 
                 −1.18 
                 0.16 
                 No 
                 No 
               
               
                 K516V 
                 −0.47 
                 0.05 
                 −0.20 
                 0.05 
                 −1.04 
                 0.11 
                 No 
                 No 
               
               
                 A517R 
                 −2.02 
                 0.07 
                 −1.56 
                 0.06 
                 −1.46 
                 0.07 
                 No 
                 No 
               
               
                 A517D 
                 −1.35 
                 0.11 
                 −0.85 
                 0.09 
                 −1.19 
                 0.18 
                 No 
                 No 
               
               
                 A517C 
                 −0.35 
                 0.08 
                 0.68 
                 0.07 
                 0.14 
                 0.17 
                 Yes 
                 No 
               
               
                 A517E 
                 −1.34 
                 0.09 
                 −1.16 
                 0.09 
                 −1.86 
                 0.16 
                 No 
                 No 
               
               
                 A517G 
                 −0.69 
                 0.03 
                 −0.65 
                 0.03 
                 −0.77 
                 0.04 
                 No 
                 No 
               
               
                 A517I 
                 0.77 
                 0.10 
                 −0.42 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A517L 
                 −0.30 
                 0.06 
                 −0.44 
                 0.06 
                 −1.22 
                 0.17 
                 No 
                 No 
               
               
                 A517M 
                 −0.50 
                 0.10 
                 −0.24 
                 0.10 
                 −0.57 
                 0.30 
                 No 
                 No 
               
               
                 A517F 
                 −0.50 
                 0.12 
                 −0.90 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A517P 
                 −0.75 
                 0.08 
                 −1.06 
                 0.09 
                 −0.86 
                 0.12 
                 No 
                 No 
               
               
                 A517S 
                 −0.28 
                 0.05 
                 −0.24 
                 0.05 
                 −0.65 
                 0.14 
                 No 
                 No 
               
               
                 A517T 
                 −0.34 
                 0.06 
                 0.06 
                 0.06 
                 −0.42 
                 0.11 
                 Yes 
                 No 
               
               
                 A517W 
                 −1.22 
                 0.07 
                 −0.27 
                 0.05 
                 −1.43 
                 0.16 
                 No 
                 No 
               
               
                 A517Y 
                 0.02 
                 0.13 
                 0.04 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A517V 
                 −0.33 
                 0.04 
                 −0.14 
                 0.04 
                 −0.44 
                 0.07 
                 No 
                 No 
               
               
                 R518K 
                 0.20 
                 0.09 
                 0.72 
                 0.08 
                 0.05 
                 0.17 
                 Yes 
                 Yes 
               
               
                 R518A 
                 −0.12 
                 0.07 
                 −0.28 
                 0.07 
                 −0.87 
                 0.24 
                 No 
                 No 
               
               
                 R518C 
                 −1.13 
                 0.12 
                 −0.21 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R518E 
                 −0.72 
                 0.10 
                 −1.08 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R518G 
                 −1.34 
                 0.05 
                 −0.78 
                 0.04 
                 −0.87 
                 0.08 
                 No 
                 No 
               
               
                 R518L 
                 −1.49 
                 0.12 
                 −1.84 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R518F 
                 −0.96 
                 0.16 
                 0.45 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R518S 
                 −0.74 
                 0.08 
                 −1.20 
                 0.09 
                 −0.73 
                 0.12 
                 No 
                 No 
               
               
                 R518* 
                 −0.33 
                 0.08 
                 −0.34 
                 0.08 
                 −0.69 
                 0.13 
                 No 
                 No 
               
               
                 R518T 
                 −0.50 
                 0.10 
                 −0.37 
                 0.10 
                 −0.40 
                 0.15 
                 No 
                 No 
               
               
                 R518W 
                 −1.01 
                 0.09 
                 −1.13 
                 0.10 
                 −1.22 
                 0.19 
                 No 
                 No 
               
               
                 R518V 
                 −0.44 
                 0.06 
                 −1.39 
                 0.09 
                 −1.43 
                 0.09 
                 No 
                 No 
               
               
                 N519A 
                 0.64 
                 0.06 
                 1.07 
                 0.06 
                 −0.06 
                 0.25 
                 Yes 
                 No 
               
               
                 N519R 
                 0.47 
                 0.05 
                 0.46 
                 0.05 
                 −0.02 
                 0.08 
                 Yes 
                 No 
               
               
                 N519D 
                 0.10 
                 0.05 
                 −0.13 
                 0.05 
                 −0.29 
                 0.07 
                 Yes 
                 No 
               
               
                 N519C 
                 0.21 
                 0.11 
                 0.23 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N519Q 
                 0.14 
                 0.12 
                 0.71 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N519E 
                 −0.66 
                 0.10 
                 −0.38 
                 0.09 
                 −0.89 
                 0.23 
                 No 
                 No 
               
               
                 N519G 
                 0.21 
                 0.04 
                 0.10 
                 0.04 
                 −0.54 
                 0.08 
                 Yes 
                 No 
               
               
                 N519H 
                 0.10 
                 0.09 
                 −0.67 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N519I 
                 0.29 
                 0.09 
                 0.18 
                 0.09 
                 −0.02 
                 0.15 
                 Yes 
                 No 
               
               
                 N519L 
                 0.28 
                 0.06 
                 0.47 
                 0.06 
                 −0.37 
                 0.08 
                 Yes 
                 No 
               
               
                 N519K 
                 −0.17 
                 0.09 
                 −0.35 
                 0.10 
                 −0.46 
                 0.19 
                 No 
                 No 
               
               
                 N519M 
                 −0.19 
                 0.10 
                 0.36 
                 0.09 
                 −0.05 
                 0.13 
                 Yes 
                 No 
               
               
                 N519F 
                 0.38 
                 0.14 
                 0.21 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N519P 
                 −0.72 
                 0.13 
                 −0.23 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N519S 
                 0.08 
                 0.05 
                 −0.03 
                 0.05 
                 0.02 
                 0.12 
                 Yes 
                 No 
               
               
                 N519T 
                 0.24 
                 0.08 
                 0.01 
                 0.09 
                 −0.37 
                 0.16 
                 Yes 
                 No 
               
               
                 N519W 
                 −0.02 
                 0.08 
                 0.38 
                 0.08 
                 −0.12 
                 0.31 
                 Yes 
                 No 
               
               
                 N519Y 
                 0.10 
                 0.12 
                 0.65 
                 0.11 
                 −0.09 
                 0.22 
                 Yes 
                 No 
               
               
                 N519V 
                 0.12 
                 0.05 
                 0.14 
                 0.05 
                 −0.39 
                 0.06 
                 Yes 
                 No 
               
               
                 Y520A 
                 −1.19 
                 0.12 
                 −0.30 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y520R 
                 −0.37 
                 0.08 
                 −1.30 
                 0.11 
                 −1.04 
                 0.24 
                 No 
                 No 
               
               
                 Y520N 
                 −0.05 
                 0.09 
                 −0.45 
                 0.10 
                 −0.62 
                 0.14 
                 No 
                 No 
               
               
                 Y520D 
                 −0.50 
                 0.12 
                 −0.04 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y520C 
                 −0.23 
                 0.07 
                 −0.24 
                 0.07 
                 −0.52 
                 0.12 
                 No 
                 No 
               
               
                 Y520E 
                 −0.61 
                 0.13 
                 −0.85 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y520G 
                 −1.91 
                 0.10 
                 −1.08 
                 0.08 
                 −1.47 
                 0.09 
                 No 
                 No 
               
               
                 Y520H 
                 0.12 
                 0.07 
                 −0.14 
                 0.07 
                 −0.34 
                 0.10 
                 Yes 
                 No 
               
               
                 Y520F 
                 0.19 
                 0.13 
                 −0.21 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y520S 
                 −0.73 
                 0.11 
                 −0.66 
                 0.11 
                 −1.13 
                 0.18 
                 No 
                 No 
               
               
                 Y520* 
                 −0.19 
                 0.07 
                 −0.42 
                 0.08 
                 −0.48 
                 0.15 
                 No 
                 No 
               
               
                 Y520W 
                 −0.38 
                 0.10 
                 0.06 
                 0.09 
                 −0.03 
                 0.16 
                 Yes 
                 No 
               
               
                 Y520V 
                 −1.45 
                 0.13 
                 −1.16 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A521D 
                 −0.72 
                 0.13 
                 −0.50 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A521C 
                 0.90 
                 0.16 
                 1.29 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A521G 
                 −0.52 
                 0.05 
                 −0.73 
                 0.06 
                 −0.98 
                 0.12 
                 No 
                 No 
               
               
                 A521L 
                 −0.61 
                 0.10 
                 −0.13 
                 0.09 
                 −0.98 
                 0.12 
                 No 
                 No 
               
               
                 A521P 
                 −0.19 
                 0.11 
                 −0.78 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A521S 
                 0.00 
                 0.09 
                 0.04 
                 0.10 
                 −0.51 
                 0.27 
                 Yes 
                 No 
               
               
                 A521T 
                 −0.23 
                 0.07 
                 0.10 
                 0.06 
                 −0.33 
                 0.11 
                 Yes 
                 No 
               
               
                 A521V 
                 −0.40 
                 0.06 
                 −0.88 
                 0.07 
                 −0.60 
                 0.13 
                 No 
                 No 
               
               
                 T522L 
                 1.10 
                 0.05 
                 0.92 
                 0.05 
                 0.28 
                 0.10 
                 Yes 
                 Yes 
               
               
                 T522M 
                 0.92 
                 0.07 
                 0.81 
                 0.08 
                 0.53 
                 0.21 
                 Yes 
                 Yes 
               
               
                 T522V 
                 0.16 
                 0.05 
                 0.28 
                 0.05 
                 0.04 
                 0.07 
                 Yes 
                 Yes 
               
               
                 T522A 
                 −0.01 
                 0.05 
                 −0.37 
                 0.06 
                 −0.55 
                 0.08 
                 No 
                 No 
               
               
                 T522R 
                 −0.17 
                 0.04 
                 0.31 
                 0.04 
                 −0.40 
                 0.12 
                 Yes 
                 No 
               
               
                 T522N 
                 0.11 
                 0.07 
                 −1.14 
                 0.11 
                 −0.50 
                 0.13 
                 Yes 
                 No 
               
               
                 T522C 
                 0.09 
                 0.08 
                 0.38 
                 0.08 
                 −0.41 
                 0.38 
                 Yes 
                 No 
               
               
                 T522Q 
                 0.71 
                 0.09 
                 0.47 
                 0.10 
                 −0.51 
                 0.36 
                 Yes 
                 No 
               
               
                 T522E 
                 −0.22 
                 0.08 
                 −1.54 
                 0.13 
                 −0.72 
                 0.27 
                 No 
                 No 
               
               
                 T522G 
                 −0.37 
                 0.04 
                 −0.18 
                 0.04 
                 −0.85 
                 0.08 
                 No 
                 No 
               
               
                 T522I 
                 0.23 
                 0.07 
                 −0.06 
                 0.08 
                 −0.11 
                 0.17 
                 Yes 
                 No 
               
               
                 T522K 
                 −0.16 
                 0.11 
                 −0.23 
                 0.11 
                 −0.67 
                 0.26 
                 No 
                 No 
               
               
                 T522F 
                 0.08 
                 0.13 
                 0.34 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T522P 
                 −1.16 
                 0.11 
                 −1.52 
                 0.14 
                 −1.14 
                 0.16 
                 No 
                 No 
               
               
                 T522S 
                 0.23 
                 0.05 
                 −0.20 
                 0.05 
                 −0.38 
                 0.10 
                 Yes 
                 No 
               
               
                 T522W 
                 −0.26 
                 0.07 
                 −0.35 
                 0.07 
                 −0.90 
                 0.13 
                 No 
                 No 
               
               
                 K523R 
                 0.17 
                 0.02 
                 0.37 
                 0.02 
                 0.00 
                 0.03 
                 Yes 
                 Yes 
               
               
                 K523A 
                 −0.19 
                 0.03 
                 0.15 
                 0.03 
                 −0.48 
                 0.09 
                 Yes 
                 No 
               
               
                 K523N 
                 −0.31 
                 0.07 
                 −0.48 
                 0.07 
                 −1.00 
                 0.08 
                 No 
                 No 
               
               
                 K523D 
                 −1.14 
                 0.07 
                 −1.35 
                 0.08 
                 −1.21 
                 0.09 
                 No 
                 No 
               
               
                 K523C 
                 −0.22 
                 0.05 
                 0.07 
                 0.04 
                 −0.81 
                 0.12 
                 Yes 
                 No 
               
               
                 K523Q 
                 −0.12 
                 0.04 
                 −0.22 
                 0.04 
                 0.01 
                 0.06 
                 Yes 
                 No 
               
               
                 K523E 
                 −0.57 
                 0.04 
                 −0.56 
                 0.04 
                 −0.86 
                 0.06 
                 No 
                 No 
               
               
                 K523G 
                 −0.16 
                 0.02 
                 0.09 
                 0.02 
                 −0.56 
                 0.03 
                 Yes 
                 No 
               
               
                 K523H 
                 −1.08 
                 0.11 
                 −0.05 
                 0.08 
                 −1.04 
                 0.28 
                 No 
                 No 
               
               
                 K523I 
                 −0.20 
                 0.07 
                 0.41 
                 0.06 
                 −1.23 
                 0.21 
                 Yes 
                 No 
               
               
                 K523L 
                 −0.78 
                 0.04 
                 −0.30 
                 0.03 
                 −0.70 
                 0.07 
                 No 
                 No 
               
               
                 K523M 
                 −0.19 
                 0.04 
                 −0.18 
                 0.04 
                 −0.52 
                 0.06 
                 No 
                 No 
               
               
                 K523F 
                 −1.08 
                 0.08 
                 −0.93 
                 0.08 
                 −1.27 
                 0.09 
                 No 
                 No 
               
               
                 K523P 
                 −1.41 
                 0.08 
                 −0.39 
                 0.06 
                 −1.21 
                 0.15 
                 No 
                 No 
               
               
                 K523S 
                 0.13 
                 0.03 
                 0.10 
                 0.03 
                 −0.36 
                 0.07 
                 Yes 
                 No 
               
               
                 K523* 
                 −1.40 
                 0.07 
                 −1.46 
                 0.08 
                 −1.19 
                 0.12 
                 No 
                 No 
               
               
                 K523T 
                 −0.19 
                 0.04 
                 −0.19 
                 0.04 
                 −0.49 
                 0.08 
                 No 
                 No 
               
               
                 K523W 
                 −0.97 
                 0.04 
                 −0.87 
                 0.04 
                 −1.41 
                 0.09 
                 No 
                 No 
               
               
                 K523Y 
                 −1.25 
                 0.10 
                 −0.43 
                 0.08 
                 −1.36 
                 0.19 
                 No 
                 No 
               
               
                 K523V 
                 −0.57 
                 0.03 
                 −0.57 
                 0.03 
                 −1.12 
                 0.08 
                 No 
                 No 
               
               
                 K524A 
                 −0.88 
                 0.09 
                 −0.32 
                 0.08 
                 −0.50 
                 0.24 
                 No 
                 No 
               
               
                 K524R 
                 −0.32 
                 0.04 
                 0.15 
                 0.04 
                 −0.28 
                 0.09 
                 Yes 
                 No 
               
               
                 K524N 
                 0.04 
                 0.04 
                 −0.48 
                 0.05 
                 −0.19 
                 0.09 
                 Yes 
                 No 
               
               
                 K524C 
                 0.06 
                 0.10 
                 0.03 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K524Q 
                 −0.42 
                 0.09 
                 −0.54 
                 0.10 
                 −0.47 
                 0.14 
                 No 
                 No 
               
               
                 K524E 
                 −0.53 
                 0.06 
                 −0.11 
                 0.06 
                 −0.49 
                 0.10 
                 No 
                 No 
               
               
                 K524G 
                 −0.43 
                 0.04 
                 −0.19 
                 0.04 
                 −0.80 
                 0.06 
                 No 
                 No 
               
               
                 K524L 
                 −0.25 
                 0.07 
                 0.32 
                 0.06 
                 −0.81 
                 0.21 
                 Yes 
                 No 
               
               
                 K524M 
                 −1.28 
                 0.15 
                 −0.75 
                 0.13 
                 −0.69 
                 0.15 
                 No 
                 No 
               
               
                 K524P 
                 −0.70 
                 0.12 
                 −0.10 
                 0.10 
                 0.02 
                 0.29 
                 Yes 
                 No 
               
               
                 K524S 
                 −0.67 
                 0.08 
                 −0.04 
                 0.07 
                 −0.73 
                 0.12 
                 No 
                 No 
               
               
                 K524* 
                 −0.92 
                 0.11 
                 −0.75 
                 0.11 
                 −0.76 
                 0.13 
                 No 
                 No 
               
               
                 K524T 
                 −0.10 
                 0.04 
                 −0.26 
                 0.04 
                 −0.15 
                 0.06 
                 No 
                 No 
               
               
                 K524W 
                 −0.58 
                 0.08 
                 −1.54 
                 0.12 
                 −1.19 
                 0.22 
                 No 
                 No 
               
               
                 K524V 
                 −0.71 
                 0.07 
                 −0.01 
                 0.06 
                 −0.68 
                 0.22 
                 No 
                 No 
               
               
                 P525A 
                 −0.21 
                 0.03 
                 0.06 
                 0.03 
                 −0.29 
                 0.07 
                 Yes 
                 No 
               
               
                 P525R 
                 −0.30 
                 0.02 
                 −0.10 
                 0.02 
                 −0.62 
                 0.05 
                 No 
                 No 
               
               
                 P525N 
                 −0.38 
                 0.09 
                 −0.35 
                 0.10 
                 −0.10 
                 0.19 
                 No 
                 No 
               
               
                 P525D 
                 0.42 
                 0.05 
                 −0.02 
                 0.05 
                 −0.30 
                 0.08 
                 Yes 
                 No 
               
               
                 P525C 
                 −0.28 
                 0.05 
                 −0.12 
                 0.05 
                 −0.48 
                 0.14 
                 No 
                 No 
               
               
                 P525Q 
                 −0.21 
                 0.06 
                 −0.19 
                 0.06 
                 −0.35 
                 0.13 
                 No 
                 No 
               
               
                 P525E 
                 −0.22 
                 0.04 
                 0.24 
                 0.04 
                 −0.30 
                 0.05 
                 Yes 
                 No 
               
               
                 P525G 
                 −0.24 
                 0.02 
                 −0.17 
                 0.02 
                 −0.51 
                 0.05 
                 No 
                 No 
               
               
                 P525H 
                 0.17 
                 0.06 
                 0.18 
                 0.07 
                 −0.24 
                 0.12 
                 Yes 
                 No 
               
               
                 P525I 
                 −0.48 
                 0.09 
                 0.06 
                 0.08 
                 0.19 
                 0.22 
                 Yes 
                 No 
               
               
                 P525L 
                 −0.37 
                 0.03 
                 0.25 
                 0.03 
                 −0.61 
                 0.06 
                 Yes 
                 No 
               
               
                 P525K 
                 −0.90 
                 0.08 
                 −1.00 
                 0.09 
                 −0.57 
                 0.17 
                 No 
                 No 
               
               
                 P525M 
                 −0.55 
                 0.06 
                 −0.18 
                 0.06 
                 −0.54 
                 0.13 
                 No 
                 No 
               
               
                 P525F 
                 −0.17 
                 0.07 
                 −0.61 
                 0.08 
                 −0.70 
                 0.16 
                 No 
                 No 
               
               
                 P525S 
                 −0.06 
                 0.03 
                 0.04 
                 0.03 
                 −0.42 
                 0.08 
                 Yes 
                 No 
               
               
                 P525* 
                 −1.61 
                 0.09 
                 −1.54 
                 0.09 
                 −1.56 
                 0.08 
                 No 
                 No 
               
               
                 P525T 
                 −0.25 
                 0.05 
                 −0.31 
                 0.05 
                 −0.45 
                 0.11 
                 No 
                 No 
               
               
                 P525W 
                 −0.25 
                 0.04 
                 −0.04 
                 0.03 
                 −0.59 
                 0.11 
                 No 
                 No 
               
               
                 P525Y 
                 −1.08 
                 0.10 
                 −1.08 
                 0.10 
                 −0.77 
                 0.08 
                 No 
                 No 
               
               
                 P525V 
                 −0.31 
                 0.03 
                 −0.08 
                 0.03 
                 −0.39 
                 0.08 
                 No 
                 No 
               
               
                 Y526A 
                 −0.28 
                 0.07 
                 0.17 
                 0.06 
                 −0.89 
                 0.19 
                 Yes 
                 No 
               
               
                 Y526R 
                 −0.71 
                 0.07 
                 −0.17 
                 0.06 
                 −1.09 
                 0.19 
                 No 
                 No 
               
               
                 Y526N 
                 −0.64 
                 0.11 
                 −0.15 
                 0.09 
                 −0.25 
                 0.17 
                 No 
                 No 
               
               
                 Y526D 
                 −0.44 
                 0.09 
                 0.07 
                 0.08 
                 −0.69 
                 0.15 
                 Yes 
                 No 
               
               
                 Y526C 
                 0.04 
                 0.06 
                 −0.03 
                 0.06 
                 −0.26 
                 0.12 
                 Yes 
                 No 
               
               
                 Y526Q 
                 −0.10 
                 0.11 
                 −0.64 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y526E 
                 −0.46 
                 0.08 
                 −0.87 
                 0.10 
                 −0.84 
                 0.21 
                 No 
                 No 
               
               
                 Y526G 
                 −0.22 
                 0.05 
                 −0.17 
                 0.05 
                 −0.65 
                 0.16 
                 No 
                 No 
               
               
                 Y526H 
                 −0.32 
                 0.08 
                 −0.25 
                 0.08 
                 −0.19 
                 0.12 
                 No 
                 No 
               
               
                 Y526I 
                 −0.40 
                 0.13 
                 −0.52 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y526L 
                 −0.53 
                 0.06 
                 −0.18 
                 0.05 
                 −0.73 
                 0.12 
                 No 
                 No 
               
               
                 Y526M 
                 −0.47 
                 0.10 
                 −0.40 
                 0.10 
                 −1.12 
                 0.27 
                 No 
                 No 
               
               
                 Y526F 
                 −0.02 
                 0.07 
                 −0.01 
                 0.07 
                 −0.44 
                 0.13 
                 No 
                 No 
               
               
                 Y526P 
                 −0.19 
                 0.10 
                 −0.88 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y526S 
                 −0.57 
                 0.06 
                 −0.68 
                 0.07 
                 −0.68 
                 0.12 
                 No 
                 No 
               
               
                 Y526* 
                 −0.42 
                 0.05 
                 −0.44 
                 0.06 
                 −0.61 
                 0.09 
                 No 
                 No 
               
               
                 Y526T 
                 −0.01 
                 0.09 
                 −0.22 
                 0.10 
                 −0.69 
                 0.21 
                 No 
                 No 
               
               
                 Y526W 
                 −1.02 
                 0.10 
                 −0.19 
                 0.08 
                 −0.32 
                 0.13 
                 No 
                 No 
               
               
                 Y526V 
                 −0.61 
                 0.05 
                 −0.14 
                 0.05 
                 −0.86 
                 0.14 
                 No 
                 No 
               
               
                 S527D 
                 0.13 
                 0.11 
                 0.01 
                 0.11 
                 0.34 
                 0.41 
                 Yes 
                 Yes 
               
               
                 S527A 
                 0.00 
                 0.06 
                 −0.37 
                 0.07 
                 −0.07 
                 0.20 
                 Yes 
                 No 
               
               
                 S527R 
                 −0.14 
                 0.04 
                 −0.73 
                 0.05 
                 −0.70 
                 0.07 
                 No 
                 No 
               
               
                 S527N 
                 −0.10 
                 0.10 
                 −0.43 
                 0.11 
                 0.01 
                 0.19 
                 Yes 
                 No 
               
               
                 S527C 
                 −0.21 
                 0.09 
                 −0.35 
                 0.09 
                 −0.10 
                 0.22 
                 No 
                 No 
               
               
                 S527Q 
                 0.09 
                 0.12 
                 −0.39 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S527E 
                 −0.49 
                 0.10 
                 0.57 
                 0.08 
                 0.03 
                 0.16 
                 Yes 
                 No 
               
               
                 S527G 
                 −0.43 
                 0.04 
                 −0.21 
                 0.04 
                 −0.53 
                 0.09 
                 No 
                 No 
               
               
                 S527H 
                 0.47 
                 0.15 
                 0.10 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S527I 
                 −1.06 
                 0.16 
                 −0.43 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S527L 
                 −0.12 
                 0.07 
                 −0.24 
                 0.07 
                 −0.44 
                 0.27 
                 No 
                 No 
               
               
                 S527K 
                 −0.09 
                 0.11 
                 −0.57 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S527P 
                 0.07 
                 0.10 
                 −0.33 
                 0.11 
                 −0.47 
                 0.36 
                 Yes 
                 No 
               
               
                 S527T 
                 0.01 
                 0.09 
                 −0.30 
                 0.10 
                 −0.22 
                 0.18 
                 Yes 
                 No 
               
               
                 S527W 
                 0.03 
                 0.07 
                 0.15 
                 0.07 
                 −0.50 
                 0.23 
                 Yes 
                 No 
               
               
                 S527Y 
                 0.31 
                 0.17 
                 0.05 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S527V 
                 −0.54 
                 0.07 
                 −0.52 
                 0.07 
                 −0.52 
                 0.10 
                 No 
                 No 
               
               
                 V528D 
                 0.01 
                 0.07 
                 0.27 
                 0.07 
                 0.12 
                 0.12 
                 Yes 
                 Yes 
               
               
                 V528L 
                 0.55 
                 0.03 
                 0.59 
                 0.03 
                 0.31 
                 0.07 
                 Yes 
                 Yes 
               
               
                 V528M 
                 0.19 
                 0.05 
                 0.02 
                 0.05 
                 0.13 
                 0.10 
                 Yes 
                 Yes 
               
               
                 V528A 
                 −0.09 
                 0.04 
                 0.29 
                 0.04 
                 −0.13 
                 0.06 
                 Yes 
                 No 
               
               
                 V528R 
                 −0.04 
                 0.04 
                 0.07 
                 0.04 
                 −0.03 
                 0.07 
                 Yes 
                 No 
               
               
                 V528N 
                 0.01 
                 0.11 
                 −0.47 
                 0.14 
                 0.31 
                 0.42 
                 Yes 
                 No 
               
               
                 V528C 
                 0.16 
                 0.07 
                 0.20 
                 0.07 
                 −0.06 
                 0.24 
                 Yes 
                 No 
               
               
                 V528Q 
                 −0.44 
                 0.09 
                 −0.29 
                 0.09 
                 0.07 
                 0.11 
                 Yes 
                 No 
               
               
                 V528E 
                 −0.66 
                 0.06 
                 0.16 
                 0.05 
                 0.00 
                 0.11 
                 Yes 
                 No 
               
               
                 V528G 
                 −0.14 
                 0.02 
                 −0.19 
                 0.02 
                 −0.19 
                 0.03 
                 No 
                 No 
               
               
                 V528H 
                 −0.62 
                 0.15 
                 1.01 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V528I 
                 0.16 
                 0.08 
                 −0.09 
                 0.09 
                 0.07 
                 0.11 
                 Yes 
                 No 
               
               
                 V528K 
                 −0.14 
                 0.08 
                 0.36 
                 0.08 
                 0.13 
                 0.14 
                 Yes 
                 No 
               
               
                 V528F 
                 −0.10 
                 0.09 
                 0.39 
                 0.08 
                 −0.59 
                 0.21 
                 Yes 
                 No 
               
               
                 V528P 
                 −0.10 
                 0.08 
                 −0.66 
                 0.10 
                 0.10 
                 0.11 
                 Yes 
                 No 
               
               
                 V528S 
                 −0.12 
                 0.05 
                 0.26 
                 0.05 
                 0.11 
                 0.06 
                 Yes 
                 No 
               
               
                 V528* 
                 −1.66 
                 0.13 
                 −1.20 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V528T 
                 0.29 
                 0.07 
                 0.00 
                 0.07 
                 0.18 
                 0.17 
                 Yes 
                 No 
               
               
                 V528W 
                 −1.31 
                 0.07 
                 −1.47 
                 0.08 
                 −0.99 
                 0.14 
                 No 
                 No 
               
               
                 V528Y 
                 −0.77 
                 0.13 
                 −0.50 
                 0.12 
                 0.24 
                 0.12 
                 Yes 
                 No 
               
               
                 E529A 
                 −0.38 
                 0.08 
                 −0.18 
                 0.08 
                 0.04 
                 0.15 
                 Yes 
                 No 
               
               
                 E529R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.70 
                 0.34 
                 Yes 
                 No 
               
               
                 E529D 
                 0.02 
                 0.07 
                 −0.61 
                 0.08 
                 0.10 
                 0.15 
                 Yes 
                 No 
               
               
                 E529Q 
                 −0.43 
                 0.14 
                 −0.49 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E529G 
                 −0.25 
                 0.05 
                 −0.16 
                 0.05 
                 −0.61 
                 0.11 
                 No 
                 No 
               
               
                 E529L 
                 −0.45 
                 0.11 
                 −0.56 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E529K 
                 0.21 
                 0.10 
                 −0.28 
                 0.11 
                 −0.65 
                 0.19 
                 Yes 
                 No 
               
               
                 E529P 
                 0.08 
                 0.15 
                 −0.30 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E529S 
                 −0.18 
                 0.11 
                 −0.08 
                 0.11 
                 −0.20 
                 0.45 
                 No 
                 No 
               
               
                 E529* 
                 −0.22 
                 0.11 
                 −0.69 
                 0.14 
                 −0.58 
                 0.17 
                 No 
                 No 
               
               
                 E529W 
                 −0.19 
                 0.13 
                 −0.11 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E529V 
                 −0.35 
                 0.06 
                 0.08 
                 0.06 
                 −0.48 
                 0.10 
                 Yes 
                 No 
               
               
                 K530A 
                 −0.96 
                 0.10 
                 −0.76 
                 0.10 
                 −0.90 
                 0.14 
                 No 
                 No 
               
               
                 K530R 
                 −0.56 
                 0.04 
                 −0.32 
                 0.04 
                 −0.59 
                 0.08 
                 No 
                 No 
               
               
                 K530N 
                 −0.78 
                 0.15 
                 −0.73 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K530C 
                 −0.10 
                 0.10 
                 −0.43 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K530Q 
                 −0.22 
                 0.05 
                 −0.56 
                 0.05 
                 −0.60 
                 0.10 
                 No 
                 No 
               
               
                 K530E 
                 −0.48 
                 0.05 
                 −0.35 
                 0.05 
                 −0.85 
                 0.09 
                 No 
                 No 
               
               
                 K530G 
                 −1.18 
                 0.07 
                 −1.09 
                 0.07 
                 −1.15 
                 0.14 
                 No 
                 No 
               
               
                 K530L 
                 −1.74 
                 0.09 
                 −1.04 
                 0.07 
                 −1.40 
                 0.14 
                 No 
                 No 
               
               
                 K530M 
                 −0.72 
                 0.07 
                 −0.42 
                 0.07 
                 −0.83 
                 0.13 
                 No 
                 No 
               
               
                 K530F 
                 −1.17 
                 0.15 
                 −0.40 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K530S 
                 −1.15 
                 0.09 
                 −0.65 
                 0.08 
                 −1.15 
                 0.13 
                 No 
                 No 
               
               
                 K530* 
                 −0.63 
                 0.07 
                 −0.43 
                 0.07 
                 −0.68 
                 0.09 
                 No 
                 No 
               
               
                 K530T 
                 −0.51 
                 0.07 
                 −0.72 
                 0.07 
                 −0.68 
                 0.10 
                 No 
                 No 
               
               
                 K530W 
                 −1.73 
                 0.12 
                 −0.35 
                 0.08 
                 −1.35 
                 0.20 
                 No 
                 No 
               
               
                 K530V 
                 −0.98 
                 0.08 
                 −1.46 
                 0.10 
                 −1.55 
                 0.23 
                 No 
                 No 
               
               
                 F531A 
                 −1.39 
                 0.13 
                 −1.72 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F531R 
                 −1.90 
                 0.12 
                 −1.41 
                 0.10 
                 −1.75 
                 0.23 
                 No 
                 No 
               
               
                 F531C 
                 −0.40 
                 0.05 
                 −0.81 
                 0.06 
                 −0.85 
                 0.09 
                 No 
                 No 
               
               
                 F531G 
                 −1.68 
                 0.08 
                 −1.22 
                 0.07 
                 −1.58 
                 0.14 
                 No 
                 No 
               
               
                 F531I 
                 −0.43 
                 0.09 
                 −0.86 
                 0.11 
                 −0.62 
                 0.11 
                 No 
                 No 
               
               
                 F531L 
                 −0.35 
                 0.05 
                 −0.40 
                 0.05 
                 −0.55 
                 0.07 
                 No 
                 No 
               
               
                 F531S 
                 −0.56 
                 0.07 
                 −0.79 
                 0.08 
                 −0.98 
                 0.11 
                 No 
                 No 
               
               
                 F531W 
                 −1.68 
                 0.13 
                 −0.86 
                 0.10 
                 −0.27 
                 0.21 
                 No 
                 No 
               
               
                 F531Y 
                 −0.99 
                 0.16 
                 −0.55 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F531V 
                 −0.22 
                 0.02 
                 −0.64 
                 0.03 
                 −0.74 
                 0.05 
                 No 
                 No 
               
               
                 K532A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.93 
                 0.19 
                 Yes 
                 No 
               
               
                 K532R 
                 −0.63 
                 0.05 
                 −0.63 
                 0.05 
                 −0.56 
                 0.10 
                 No 
                 No 
               
               
                 K532N 
                 −0.39 
                 0.11 
                 −0.71 
                 0.13 
                 −0.45 
                 0.12 
                 No 
                 No 
               
               
                 K532Q 
                 −0.42 
                 0.08 
                 −0.74 
                 0.10 
                 −0.96 
                 0.11 
                 No 
                 No 
               
               
                 K532E 
                 −0.49 
                 0.05 
                 −0.38 
                 0.05 
                 −0.64 
                 0.12 
                 No 
                 No 
               
               
                 K532G 
                 −1.74 
                 0.08 
                 −1.15 
                 0.07 
                 −1.35 
                 0.11 
                 No 
                 No 
               
               
                 K532L 
                 −1.28 
                 0.11 
                 −1.26 
                 0.11 
                 −1.36 
                 0.21 
                 No 
                 No 
               
               
                 K532M 
                 −0.48 
                 0.09 
                 −0.58 
                 0.10 
                 −0.65 
                 0.09 
                 No 
                 No 
               
               
                 K532S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.93 
                 0.25 
                 Yes 
                 No 
               
               
                 K532* 
                 −0.42 
                 0.06 
                 −0.27 
                 0.06 
                 −0.65 
                 0.12 
                 No 
                 No 
               
               
                 K532T 
                 −0.37 
                 0.06 
                 −1.05 
                 0.07 
                 −0.52 
                 0.10 
                 No 
                 No 
               
               
                 K532V 
                 −1.99 
                 0.11 
                 −1.32 
                 0.09 
                 −1.19 
                 0.12 
                 No 
                 No 
               
               
                 L533R 
                 −0.17 
                 0.04 
                 −0.41 
                 0.04 
                 −0.57 
                 0.08 
                 No 
                 No 
               
               
                 L533G 
                 −1.82 
                 0.14 
                 −1.54 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L533M 
                 −0.36 
                 0.12 
                 −0.29 
                 0.12 
                 −0.12 
                 0.17 
                 No 
                 No 
               
               
                 L533P 
                 −0.18 
                 0.07 
                 −0.06 
                 0.07 
                 −0.28 
                 0.12 
                 No 
                 No 
               
               
                 L533V 
                 −1.49 
                 0.12 
                 −0.64 
                 0.09 
                 −0.58 
                 0.19 
                 No 
                 No 
               
               
                 N534A 
                 −1.49 
                 0.08 
                 −1.30 
                 0.08 
                 −0.31 
                 0.09 
                 No 
                 No 
               
               
                 N534R 
                 −1.13 
                 0.05 
                 −1.37 
                 0.06 
                 −0.52 
                 0.04 
                 No 
                 No 
               
               
                 N534D 
                 −1.07 
                 0.08 
                 −0.72 
                 0.07 
                 −0.75 
                 0.11 
                 No 
                 No 
               
               
                 N534C 
                 −1.50 
                 0.13 
                 −1.27 
                 0.12 
                 0.19 
                 0.20 
                 Yes 
                 No 
               
               
                 N534Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.67 
                 0.24 
                 Yes 
                 No 
               
               
                 N534E 
                 −2.05 
                 0.10 
                 −1.48 
                 0.08 
                 −1.32 
                 0.13 
                 No 
                 No 
               
               
                 N534G 
                 −1.43 
                 0.04 
                 −0.96 
                 0.04 
                 −1.10 
                 0.04 
                 No 
                 No 
               
               
                 N534H 
                 −0.18 
                 0.03 
                 −0.50 
                 0.04 
                 −0.20 
                 0.06 
                 No 
                 No 
               
               
                 N534I 
                 −0.54 
                 0.08 
                 0.00 
                 0.07 
                 −0.60 
                 0.18 
                 Yes 
                 No 
               
               
                 N534L 
                 −1.92 
                 0.11 
                 −1.79 
                 0.11 
                 −0.26 
                 0.07 
                 No 
                 No 
               
               
                 N534K 
                 −1.00 
                 0.07 
                 −0.74 
                 0.07 
                 −0.01 
                 0.10 
                 No 
                 No 
               
               
                 N534M 
                 −1.72 
                 0.12 
                 −0.90 
                 0.09 
                 0.88 
                 0.19 
                 Yes 
                 No 
               
               
                 N534F 
                 0.11 
                 0.10 
                 −1.16 
                 0.16 
                 0.16 
                 0.30 
                 Yes 
                 No 
               
               
                 N534P 
                 −0.33 
                 0.07 
                 −0.26 
                 0.07 
                 −1.27 
                 0.16 
                 No 
                 No 
               
               
                 N534S 
                 −1.00 
                 0.06 
                 −0.72 
                 0.06 
                 0.22 
                 0.05 
                 Yes 
                 No 
               
               
                 N534* 
                 −1.20 
                 0.09 
                 −2.22 
                 0.15 
                 −1.84 
                 0.10 
                 No 
                 No 
               
               
                 N534T 
                 −0.38 
                 0.04 
                 −0.40 
                 0.04 
                 0.49 
                 0.06 
                 Yes 
                 No 
               
               
                 N534W 
                 −1.54 
                 0.08 
                 −0.69 
                 0.06 
                 −0.29 
                 0.07 
                 No 
                 No 
               
               
                 N534Y 
                 −0.97 
                 0.12 
                 −0.47 
                 0.10 
                 −0.57 
                 0.17 
                 No 
                 No 
               
               
                 N534V 
                 −1.35 
                 0.07 
                 −1.17 
                 0.06 
                 −0.59 
                 0.06 
                 No 
                 No 
               
               
                 N534A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.33 
                 0.09 
                 Yes 
                 No 
               
               
                 N534R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.55 
                 0.04 
                 Yes 
                 No 
               
               
                 N534D 
                 −0.11 
                 0.09 
                 −0.10 
                 0.09 
                 −0.69 
                 0.10 
                 No 
                 No 
               
               
                 N534C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.16 
                 0.19 
                 Yes 
                 No 
               
               
                 N534Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.72 
                 0.24 
                 Yes 
                 No 
               
               
                 N534E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.34 
                 0.13 
                 Yes 
                 No 
               
               
                 N534G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.11 
                 0.04 
                 Yes 
                 No 
               
               
                 N534H 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.19 
                 0.24 
                 Yes 
                 No 
               
               
                 N534I 
                 −0.14 
                 0.19 
                 −0.05 
                 0.19 
                 −0.61 
                 0.19 
                 No 
                 No 
               
               
                 N534L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.22 
                 0.07 
                 Yes 
                 No 
               
               
                 N534K 
                 −0.47 
                 0.14 
                 −0.26 
                 0.13 
                 −0.06 
                 0.09 
                 No 
                 No 
               
               
                 N534M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.83 
                 0.18 
                 Yes 
                 No 
               
               
                 N534F 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.26 
                 0.30 
                 Yes 
                 No 
               
               
                 N534S 
                 −0.15 
                 0.07 
                 −0.03 
                 0.07 
                 0.20 
                 0.05 
                 Yes 
                 No 
               
               
                 N534* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.73 
                 0.10 
                 Yes 
                 No 
               
               
                 N534T 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.91 
                 0.15 
                 Yes 
                 No 
               
               
                 N534W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.32 
                 0.07 
                 Yes 
                 No 
               
               
                 N534Y 
                 −0.01 
                 0.13 
                 0.04 
                 0.13 
                 −0.53 
                 0.16 
                 Yes 
                 No 
               
               
                 N534V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.57 
                 0.06 
                 Yes 
                 No 
               
               
                 F535A 
                 −1.29 
                 0.08 
                 −1.38 
                 0.09 
                 −1.53 
                 0.15 
                 No 
                 No 
               
               
                 F535R 
                 −2.11 
                 0.10 
                 −1.42 
                 0.08 
                 −1.73 
                 0.13 
                 No 
                 No 
               
               
                 F535C 
                 −0.48 
                 0.06 
                 −0.52 
                 0.06 
                 −0.79 
                 0.05 
                 No 
                 No 
               
               
                 F535E 
                 −2.40 
                 0.14 
                 −1.29 
                 0.09 
                 −1.54 
                 0.09 
                 No 
                 No 
               
               
                 F535G 
                 −1.68 
                 0.06 
                 −1.41 
                 0.05 
                 −1.60 
                 0.04 
                 No 
                 No 
               
               
                 F535I 
                 −0.99 
                 0.13 
                 −0.63 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F535L 
                 −0.97 
                 0.06 
                 −0.52 
                 0.05 
                 −0.92 
                 0.05 
                 No 
                 No 
               
               
                 F535M 
                 −0.78 
                 0.11 
                 −0.99 
                 0.13 
                 −0.68 
                 0.24 
                 No 
                 No 
               
               
                 F535S 
                 −0.91 
                 0.06 
                 −0.54 
                 0.06 
                 −1.11 
                 0.09 
                 No 
                 No 
               
               
                 F535W 
                 −2.13 
                 0.11 
                 −1.41 
                 0.09 
                 −1.73 
                 0.15 
                 No 
                 No 
               
               
                 F535Y 
                 −0.65 
                 0.10 
                 −0.50 
                 0.10 
                 −0.62 
                 0.16 
                 No 
                 No 
               
               
                 F535V 
                 −0.87 
                 0.04 
                 −1.00 
                 0.05 
                 −0.98 
                 0.04 
                 No 
                 No 
               
               
                 F535A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.47 
                 0.15 
                 Yes 
                 No 
               
               
                 F535R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.74 
                 0.12 
                 Yes 
                 No 
               
               
                 F535C 
                 −0.09 
                 0.06 
                 0.09 
                 0.05 
                 −0.54 
                 0.06 
                 Yes 
                 No 
               
               
                 F535E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.65 
                 0.09 
                 Yes 
                 No 
               
               
                 F535G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.93 
                 0.04 
                 Yes 
                 No 
               
               
                 F535L 
                 −0.04 
                 0.06 
                 0.03 
                 0.06 
                 −0.69 
                 0.05 
                 Yes 
                 No 
               
               
                 F535M 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.67 
                 0.21 
                 Yes 
                 No 
               
               
                 F535S 
                 −0.14 
                 0.08 
                 0.00 
                 0.08 
                 −1.14 
                 0.09 
                 No 
                 No 
               
               
                 F535W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.68 
                 0.14 
                 Yes 
                 No 
               
               
                 F535Y 
                 −0.19 
                 0.12 
                 −0.06 
                 0.12 
                 −0.53 
                 0.17 
                 No 
                 No 
               
               
                 F535V 
                 −0.05 
                 0.05 
                 −0.01 
                 0.05 
                 −0.76 
                 0.06 
                 No 
                 No 
               
               
                 Q536A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.02 
                 0.19 
                 Yes 
                 No 
               
               
                 Q536R 
                 0.02 
                 0.08 
                 −0.02 
                 0.09 
                 0.08 
                 0.05 
                 Yes 
                 No 
               
               
                 Q536D 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.23 
                 0.28 
                 Yes 
                 No 
               
               
                 Q536C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.02 
                 0.28 
                 Yes 
                 No 
               
               
                 Q536E 
                 0.00 
                 0.16 
                 0.02 
                 0.16 
                 −0.66 
                 0.08 
                 Yes 
                 No 
               
               
                 Q536G 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.22 
                 0.05 
                 Yes 
                 No 
               
               
                 Q536H 
                 −0.05 
                 0.19 
                 −0.05 
                 0.19 
                 −0.34 
                 0.22 
                 No 
                 No 
               
               
                 Q536L 
                 −0.10 
                 0.15 
                 −0.11 
                 0.15 
                 −1.09 
                 0.14 
                 No 
                 No 
               
               
                 Q536K 
                 0.56 
                 0.09 
                 −0.36 
                 0.11 
                 −0.09 
                 0.13 
                 Yes 
                 No 
               
               
                 Q536S 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.60 
                 0.09 
                 Yes 
                 No 
               
               
                 Q536* 
                 0.15 
                 0.09 
                 0.03 
                 0.10 
                 −0.74 
                 0.10 
                 Yes 
                 No 
               
               
                 Q536V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.88 
                 0.09 
                 Yes 
                 No 
               
               
                 R537A 
                 −1.11 
                 0.10 
                 −1.99 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537Q 
                 −0.56 
                 0.13 
                 −1.08 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537E 
                 −1.40 
                 0.13 
                 −1.33 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537G 
                 −1.10 
                 0.05 
                 −1.07 
                 0.05 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537L 
                 −1.50 
                 0.13 
                 −1.38 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537K 
                 −0.58 
                 0.09 
                 −0.81 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537M 
                 −1.57 
                 0.02 
                 −1.19 
                 0.02 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537S 
                 −1.30 
                 0.11 
                 −0.65 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537W 
                 −1.42 
                 0.10 
                 −1.60 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R537V 
                 −1.52 
                 0.11 
                 −1.85 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M537A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.52 
                 0.24 
                 Yes 
                 No 
               
               
                 M537R 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.70 
                 0.04 
                 Yes 
                 No 
               
               
                 M537G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.55 
                 0.08 
                 Yes 
                 No 
               
               
                 M537I 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.01 
                 0.15 
                 Yes 
                 No 
               
               
                 M537L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.09 
                 0.13 
                 Yes 
                 No 
               
               
                 M537K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.19 
                 0.14 
                 Yes 
                 No 
               
               
                 M537T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.29 
                 0.13 
                 Yes 
                 No 
               
               
                 M537W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.30 
                 0.19 
                 Yes 
                 No 
               
               
                 M537V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.62 
                 0.10 
                 Yes 
                 No 
               
               
                 P538A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.19 
                 0.06 
                 Yes 
                 No 
               
               
                 P538R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.72 
                 0.08 
                 Yes 
                 No 
               
               
                 P538Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.46 
                 0.11 
                 Yes 
                 No 
               
               
                 P538E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.79 
                 0.22 
                 Yes 
                 No 
               
               
                 P538G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.67 
                 0.09 
                 Yes 
                 No 
               
               
                 P538H 
                 −0.20 
                 0.17 
                 −0.19 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P538L 
                 −0.23 
                 0.12 
                 −0.09 
                 0.11 
                 −1.49 
                 0.05 
                 No 
                 No 
               
               
                 P538S 
                 0.19 
                 0.12 
                 0.18 
                 0.12 
                 −1.47 
                 0.11 
                 Yes 
                 No 
               
               
                 P538T 
                 −0.08 
                 0.06 
                 0.13 
                 0.06 
                 −0.38 
                 0.06 
                 Yes 
                 No 
               
               
                 P538W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.82 
                 0.17 
                 Yes 
                 No 
               
               
                 P538V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.71 
                 0.14 
                 Yes 
                 No 
               
               
                 T539A 
                 0.08 
                 0.07 
                 −0.03 
                 0.08 
                 −1.10 
                 0.06 
                 Yes 
                 No 
               
               
                 T539R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.51 
                 0.10 
                 Yes 
                 No 
               
               
                 T539N 
                 0.16 
                 0.14 
                 0.06 
                 0.15 
                 −1.00 
                 0.17 
                 Yes 
                 No 
               
               
                 T539C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.11 
                 0.14 
                 Yes 
                 No 
               
               
                 T539Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.19 
                 0.20 
                 Yes 
                 No 
               
               
                 T539E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.61 
                 0.12 
                 Yes 
                 No 
               
               
                 T539G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.63 
                 0.05 
                 Yes 
                 No 
               
               
                 T539I 
                 −0.20 
                 0.13 
                 0.00 
                 0.13 
                 −1.04 
                 0.16 
                 No 
                 No 
               
               
                 T539L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −2.07 
                 0.13 
                 Yes 
                 No 
               
               
                 T539K 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.23 
                 0.26 
                 Yes 
                 No 
               
               
                 T539M 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.64 
                 0.18 
                 Yes 
                 No 
               
               
                 T539P 
                 −0.33 
                 0.14 
                 −0.40 
                 0.14 
                 −1.51 
                 0.14 
                 No 
                 No 
               
               
                 T539S 
                 −0.03 
                 0.05 
                 −0.17 
                 0.05 
                 −0.14 
                 0.04 
                 No 
                 No 
               
               
                 T539V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.65 
                 0.11 
                 Yes 
                 No 
               
               
                 L540R 
                 −0.17 
                 0.15 
                 −0.30 
                 0.15 
                 −1.27 
                 0.14 
                 No 
                 No 
               
               
                 L540Q 
                 0.12 
                 0.08 
                 0.13 
                 0.08 
                 −0.05 
                 0.08 
                 Yes 
                 No 
               
               
                 L540G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.83 
                 0.13 
                 Yes 
                 No 
               
               
                 L540M 
                 0.04 
                 0.08 
                 −0.02 
                 0.09 
                 −0.13 
                 0.07 
                 Yes 
                 No 
               
               
                 L540P 
                 0.05 
                 0.09 
                 0.09 
                 0.09 
                 −0.40 
                 0.13 
                 Yes 
                 No 
               
               
                 L540V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.58 
                 0.24 
                 Yes 
                 No 
               
               
                 A541R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.71 
                 0.09 
                 Yes 
                 No 
               
               
                 A541D 
                 0.11 
                 0.12 
                 0.35 
                 0.11 
                 −0.22 
                 0.06 
                 Yes 
                 No 
               
               
                 A541C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.02 
                 0.39 
                 Yes 
                 No 
               
               
                 A541G 
                 0.38 
                 0.07 
                 0.36 
                 0.07 
                 −0.06 
                 0.12 
                 Yes 
                 No 
               
               
                 A541L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.32 
                 0.23 
                 Yes 
                 No 
               
               
                 A541S 
                 −0.11 
                 0.15 
                 −0.14 
                 0.15 
                 −1.66 
                 0.14 
                 No 
                 No 
               
               
                 A541T 
                 −0.11 
                 0.05 
                 −0.11 
                 0.05 
                 −0.50 
                 0.12 
                 No 
                 No 
               
               
                 A541V 
                 −0.06 
                 0.09 
                 0.00 
                 0.09 
                 −0.77 
                 0.12 
                 No 
                 No 
               
               
                 S542N 
                 0.24 
                 0.09 
                 0.02 
                 0.09 
                 0.29 
                 0.07 
                 Yes 
                 Yes 
               
               
                 S542C 
                 0.03 
                 0.17 
                 0.15 
                 0.17 
                 0.42 
                 0.16 
                 Yes 
                 Yes 
               
               
                 S542A 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.79 
                 0.05 
                 Yes 
                 No 
               
               
                 S542R 
                 −0.37 
                 0.10 
                 −0.13 
                 0.10 
                 1.34 
                 0.04 
                 Yes 
                 No 
               
               
                 S542D 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.70 
                 0.14 
                 Yes 
                 No 
               
               
                 S542Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.04 
                 0.23 
                 Yes 
                 No 
               
               
                 S542E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.68 
                 0.07 
                 Yes 
                 No 
               
               
                 S542G 
                 0.23 
                 0.07 
                 −0.10 
                 0.08 
                 −0.79 
                 0.06 
                 Yes 
                 No 
               
               
                 S542H 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.08 
                 0.35 
                 Yes 
                 No 
               
               
                 S542I 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.13 
                 0.32 
                 Yes 
                 No 
               
               
                 S542L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.67 
                 0.10 
                 Yes 
                 No 
               
               
                 S542K 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.36 
                 0.09 
                 Yes 
                 No 
               
               
                 S542M 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.10 
                 0.11 
                 Yes 
                 No 
               
               
                 S542P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.85 
                 0.27 
                 Yes 
                 No 
               
               
                 S542T 
                 0.68 
                 0.17 
                 0.24 
                 0.19 
                 −0.08 
                 0.10 
                 Yes 
                 No 
               
               
                 S542W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.34 
                 0.06 
                 Yes 
                 No 
               
               
                 S542V 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.38 
                 0.08 
                 Yes 
                 No 
               
               
                 G543A 
                 −2.33 
                 0.07 
                 −1.64 
                 0.05 
                 −2.12 
                 0.10 
                 No 
                 No 
               
               
                 G543R 
                 −1.78 
                 0.05 
                 −1.75 
                 0.05 
                 −1.89 
                 0.07 
                 No 
                 No 
               
               
                 G543D 
                 −1.02 
                 0.07 
                 −1.88 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G543C 
                 −0.32 
                 0.04 
                 −0.29 
                 0.04 
                 −0.07 
                 0.06 
                 No 
                 No 
               
               
                 G543E 
                 −2.56 
                 0.11 
                 −1.80 
                 0.08 
                 −2.09 
                 0.18 
                 No 
                 No 
               
               
                 G543I 
                 −1.30 
                 0.14 
                 −1.24 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G543L 
                 −1.74 
                 0.08 
                 −1.17 
                 0.06 
                 −1.85 
                 0.22 
                 No 
                 No 
               
               
                 G543F 
                 −0.91 
                 0.09 
                 −0.77 
                 0.08 
                 −0.93 
                 0.14 
                 No 
                 No 
               
               
                 G543P 
                 −1.28 
                 0.08 
                 −1.18 
                 0.08 
                 −1.40 
                 0.22 
                 No 
                 No 
               
               
                 G543S 
                 −1.21 
                 0.05 
                 −1.22 
                 0.05 
                 −1.63 
                 0.08 
                 No 
                 No 
               
               
                 G543* 
                 −1.66 
                 0.13 
                 −1.93 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G543W 
                 −1.55 
                 0.08 
                 −1.49 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G543V 
                 −0.80 
                 0.03 
                 −0.81 
                 0.03 
                 −0.80 
                 0.06 
                 No 
                 No 
               
               
                 W544A 
                 −1.17 
                 0.05 
                 −1.90 
                 0.06 
                 −1.67 
                 0.09 
                 No 
                 No 
               
               
                 W544R 
                 −1.30 
                 0.03 
                 −1.40 
                 0.03 
                 −1.35 
                 0.04 
                 No 
                 No 
               
               
                 W544N 
                 −1.11 
                 0.10 
                 −1.78 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 W544D 
                 −1.61 
                 0.09 
                 −1.58 
                 0.09 
                 −1.51 
                 0.14 
                 No 
                 No 
               
               
                 W544C 
                 −0.88 
                 0.06 
                 −1.34 
                 0.07 
                 −1.21 
                 0.10 
                 No 
                 No 
               
               
                 W544Q 
                 −1.24 
                 0.08 
                 −1.17 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 W544E 
                 −1.14 
                 0.05 
                 −1.44 
                 0.05 
                 −1.54 
                 0.06 
                 No 
                 No 
               
               
                 W544G 
                 −1.68 
                 0.03 
                 −1.47 
                 0.03 
                 −1.55 
                 0.04 
                 No 
                 No 
               
               
                 W544H 
                 −0.01 
                 0.08 
                 −1.46 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 W544L 
                 −1.76 
                 0.06 
                 −1.40 
                 0.05 
                 −1.41 
                 0.04 
                 No 
                 No 
               
               
                 W544K 
                 −2.26 
                 0.11 
                 −1.33 
                 0.07 
                 −1.39 
                 0.08 
                 No 
                 No 
               
               
                 W544M 
                 −2.09 
                 0.11 
                 −1.42 
                 0.08 
                 −1.45 
                 0.15 
                 No 
                 No 
               
               
                 W544F 
                 −0.96 
                 0.09 
                 −1.72 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 W544P 
                 −1.84 
                 0.09 
                 −1.34 
                 0.08 
                 −1.51 
                 0.09 
                 No 
                 No 
               
               
                 W544S 
                 −0.66 
                 0.03 
                 −0.59 
                 0.03 
                 −0.57 
                 0.03 
                 No 
                 No 
               
               
                 W544* 
                 −0.85 
                 0.05 
                 −1.05 
                 0.05 
                 −1.09 
                 0.07 
                 No 
                 No 
               
               
                 W544T 
                 −1.81 
                 0.09 
                 −1.08 
                 0.07 
                 −1.83 
                 0.17 
                 No 
                 No 
               
               
                 W544V 
                 −1.60 
                 0.05 
                 −1.52 
                 0.05 
                 −1.52 
                 0.09 
                 No 
                 No 
               
               
                 D545A 
                 −1.34 
                 0.06 
                 −1.18 
                 0.06 
                 −1.75 
                 0.13 
                 No 
                 No 
               
               
                 D545R 
                 −2.22 
                 0.08 
                 −1.82 
                 0.06 
                 −1.53 
                 0.12 
                 No 
                 No 
               
               
                 D545N 
                 −1.00 
                 0.10 
                 −0.89 
                 0.09 
                 −1.05 
                 0.15 
                 No 
                 No 
               
               
                 D545C 
                 −2.14 
                 0.13 
                 −1.41 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545E 
                 −1.54 
                 0.07 
                 −2.07 
                 0.09 
                 −1.66 
                 0.14 
                 No 
                 No 
               
               
                 D545G 
                 −1.30 
                 0.04 
                 −1.13 
                 0.04 
                 −1.44 
                 0.07 
                 No 
                 No 
               
               
                 D545H 
                 −1.20 
                 0.14 
                 −0.72 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545L 
                 −1.77 
                 0.08 
                 −1.23 
                 0.06 
                 −1.75 
                 0.21 
                 No 
                 No 
               
               
                 D545K 
                 −1.83 
                 0.15 
                 −1.54 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545M 
                 −1.30 
                 0.11 
                 −0.90 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545P 
                 −1.73 
                 0.12 
                 −1.07 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545S 
                 −0.99 
                 0.06 
                 −0.97 
                 0.06 
                 −1.65 
                 0.18 
                 No 
                 No 
               
               
                 D545T 
                 −2.02 
                 0.14 
                 −1.36 
                 0.10 
                 −1.24 
                 0.25 
                 No 
                 No 
               
               
                 D545W 
                 −2.52 
                 0.12 
                 −2.44 
                 0.12 
                 −1.79 
                 0.16 
                 No 
                 No 
               
               
                 D545Y 
                 −1.34 
                 0.12 
                 −1.40 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D545V 
                 −1.90 
                 0.07 
                 −1.31 
                 0.05 
                 −1.58 
                 0.10 
                 No 
                 No 
               
               
                 V546A 
                 0.05 
                 0.04 
                 −0.28 
                 0.04 
                 −1.03 
                 0.08 
                 Yes 
                 No 
               
               
                 V546R 
                 −0.34 
                 0.04 
                 −0.10 
                 0.04 
                 −0.24 
                 0.05 
                 No 
                 No 
               
               
                 V546D 
                 −1.89 
                 0.14 
                 −0.98 
                 0.10 
                 −1.80 
                 0.23 
                 No 
                 No 
               
               
                 V546C 
                 −0.63 
                 0.08 
                 0.12 
                 0.06 
                 −1.17 
                 0.18 
                 Yes 
                 No 
               
               
                 V546Q 
                 −0.14 
                 0.09 
                 −0.04 
                 0.08 
                 −0.37 
                 0.22 
                 No 
                 No 
               
               
                 V546E 
                 −0.85 
                 0.06 
                 −0.72 
                 0.06 
                 −1.16 
                 0.10 
                 No 
                 No 
               
               
                 V546G 
                 −0.89 
                 0.03 
                 −0.75 
                 0.03 
                 −1.38 
                 0.06 
                 No 
                 No 
               
               
                 V546I 
                 0.17 
                 0.09 
                 −0.21 
                 0.10 
                 −0.01 
                 0.36 
                 Yes 
                 No 
               
               
                 V546L 
                 −0.09 
                 0.04 
                 −0.03 
                 0.04 
                 −0.77 
                 0.12 
                 No 
                 No 
               
               
                 V546K 
                 −0.23 
                 0.09 
                 −0.07 
                 0.09 
                 −0.28 
                 0.09 
                 No 
                 No 
               
               
                 V546M 
                 −0.48 
                 0.06 
                 −0.39 
                 0.06 
                 −0.14 
                 0.11 
                 No 
                 No 
               
               
                 V546F 
                 −0.58 
                 0.10 
                 −1.20 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V546S 
                 −0.24 
                 0.05 
                 −0.75 
                 0.06 
                 −1.19 
                 0.07 
                 No 
                 No 
               
               
                 V546* 
                 −1.55 
                 0.12 
                 −1.19 
                 0.10 
                 −1.56 
                 0.23 
                 No 
                 No 
               
               
                 V546T 
                 0.15 
                 0.07 
                 −0.59 
                 0.09 
                 −0.82 
                 0.09 
                 Yes 
                 No 
               
               
                 V546W 
                 −1.75 
                 0.08 
                 −1.06 
                 0.06 
                 −1.43 
                 0.15 
                 No 
                 No 
               
               
                 V546Y 
                 0.40 
                 0.10 
                 −0.50 
                 0.13 
                 −0.45 
                 0.39 
                 Yes 
                 No 
               
               
                 N547A 
                 −0.97 
                 0.06 
                 −0.81 
                 0.06 
                 −1.74 
                 0.12 
                 No 
                 No 
               
               
                 N547R 
                 −0.75 
                 0.04 
                 −0.98 
                 0.05 
                 −1.25 
                 0.05 
                 No 
                 No 
               
               
                 N547D 
                 −1.06 
                 0.08 
                 −0.98 
                 0.08 
                 −1.08 
                 0.12 
                 No 
                 No 
               
               
                 N547E 
                 −1.13 
                 0.07 
                 −1.64 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N547G 
                 −0.99 
                 0.04 
                 −1.38 
                 0.05 
                 −1.68 
                 0.04 
                 No 
                 No 
               
               
                 N547I 
                 −0.57 
                 0.10 
                 −0.69 
                 0.10 
                 −0.97 
                 0.15 
                 No 
                 No 
               
               
                 N547L 
                 −2.14 
                 0.12 
                 −1.01 
                 0.07 
                 −1.56 
                 0.18 
                 No 
                 No 
               
               
                 N547K 
                 −0.72 
                 0.08 
                 −0.48 
                 0.07 
                 −0.83 
                 0.12 
                 No 
                 No 
               
               
                 N547S 
                 −0.69 
                 0.06 
                 −0.98 
                 0.06 
                 −1.07 
                 0.09 
                 No 
                 No 
               
               
                 N547T 
                 −2.13 
                 0.13 
                 −1.62 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N547W 
                 −1.69 
                 0.09 
                 −1.84 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N547Y 
                 −0.39 
                 0.10 
                 −0.94 
                 0.12 
                 −1.04 
                 0.21 
                 No 
                 No 
               
               
                 N547V 
                 −1.63 
                 0.07 
                 −1.46 
                 0.07 
                 −1.86 
                 0.15 
                 No 
                 No 
               
               
                 K548A 
                 −1.24 
                 0.04 
                 −1.12 
                 0.04 
                 −1.74 
                 0.03 
                 No 
                 No 
               
               
                 K548R 
                 −0.59 
                 0.02 
                 −0.51 
                 0.02 
                 −0.18 
                 0.03 
                 No 
                 No 
               
               
                 K548N 
                 −0.98 
                 0.07 
                 −1.11 
                 0.08 
                 −1.10 
                 0.09 
                 No 
                 No 
               
               
                 K548D 
                 −2.69 
                 0.13 
                 −1.63 
                 0.08 
                 −2.01 
                 0.14 
                 No 
                 No 
               
               
                 K548C 
                 −0.97 
                 0.06 
                 −0.64 
                 0.05 
                 −1.44 
                 0.14 
                 No 
                 No 
               
               
                 K548Q 
                 −0.31 
                 0.04 
                 −0.24 
                 0.04 
                 −0.41 
                 0.06 
                 No 
                 No 
               
               
                 K548E 
                 −1.54 
                 0.05 
                 −1.45 
                 0.05 
                 −1.51 
                 0.04 
                 No 
                 No 
               
               
                 K548G 
                 −1.14 
                 0.02 
                 −0.95 
                 0.02 
                 −1.61 
                 0.02 
                 No 
                 No 
               
               
                 K548H 
                 −1.58 
                 0.14 
                 −1.58 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K548I 
                 −1.05 
                 0.07 
                 −1.27 
                 0.08 
                 −0.98 
                 0.06 
                 No 
                 No 
               
               
                 K548L 
                 −1.72 
                 0.06 
                 −1.56 
                 0.05 
                 −1.96 
                 0.08 
                 No 
                 No 
               
               
                 K548M 
                 −0.27 
                 0.04 
                 −0.19 
                 0.04 
                 −1.10 
                 0.10 
                 No 
                 No 
               
               
                 K548F 
                 −2.01 
                 0.12 
                 −1.60 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K548P 
                 −1.78 
                 0.09 
                 −1.04 
                 0.07 
                 −1.86 
                 0.16 
                 No 
                 No 
               
               
                 K548S 
                 −0.97 
                 0.04 
                 −0.55 
                 0.03 
                 −1.40 
                 0.08 
                 No 
                 No 
               
               
                 K548* 
                 −1.65 
                 0.08 
                 −0.85 
                 0.06 
                 −1.40 
                 0.13 
                 No 
                 No 
               
               
                 K548T 
                 −0.12 
                 0.04 
                 −0.74 
                 0.05 
                 −1.19 
                 0.07 
                 No 
                 No 
               
               
                 K548W 
                 −2.13 
                 0.07 
                 −1.65 
                 0.05 
                 −1.44 
                 0.07 
                 No 
                 No 
               
               
                 K548Y 
                 −1.07 
                 0.09 
                 −1.63 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K548V 
                 −0.72 
                 0.03 
                 −0.39 
                 0.03 
                 −0.97 
                 0.05 
                 No 
                 No 
               
               
                 E549A 
                 −1.80 
                 0.06 
                 −1.49 
                 0.05 
                 −1.69 
                 0.07 
                 No 
                 No 
               
               
                 E549R 
                 −1.64 
                 0.05 
                 −1.69 
                 0.05 
                 −1.80 
                 0.09 
                 No 
                 No 
               
               
                 E549D 
                 −1.63 
                 0.09 
                 −1.13 
                 0.07 
                 −1.53 
                 0.14 
                 No 
                 No 
               
               
                 E549C 
                 −2.08 
                 0.12 
                 −1.84 
                 0.11 
                 −1.56 
                 0.18 
                 No 
                 No 
               
               
                 E549Q 
                 −0.41 
                 0.05 
                 −0.41 
                 0.05 
                 −0.80 
                 0.10 
                 No 
                 No 
               
               
                 E549G 
                 −1.50 
                 0.03 
                 −1.53 
                 0.03 
                 −1.60 
                 0.04 
                 No 
                 No 
               
               
                 E549I 
                 −1.07 
                 0.12 
                 −1.12 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E549L 
                 −1.62 
                 0.07 
                 −1.31 
                 0.06 
                 −1.65 
                 0.13 
                 No 
                 No 
               
               
                 E549K 
                 −0.91 
                 0.07 
                 −0.89 
                 0.07 
                 −0.99 
                 0.08 
                 No 
                 No 
               
               
                 E549M 
                 −2.06 
                 0.12 
                 −1.66 
                 0.10 
                 −1.57 
                 0.17 
                 No 
                 No 
               
               
                 E549F 
                 −1.59 
                 0.14 
                 −1.27 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E549S 
                 −2.21 
                 0.08 
                 −1.69 
                 0.07 
                 −1.91 
                 0.05 
                 No 
                 No 
               
               
                 E549* 
                 −1.66 
                 0.09 
                 −1.47 
                 0.09 
                 −1.59 
                 0.14 
                 No 
                 No 
               
               
                 E549T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.39 
                 0.10 
                 Yes 
                 No 
               
               
                 E549W 
                 −0.99 
                 0.05 
                 −1.72 
                 0.07 
                 −1.85 
                 0.11 
                 No 
                 No 
               
               
                 E549V 
                 −1.01 
                 0.04 
                 −0.79 
                 0.04 
                 −1.37 
                 0.04 
                 No 
                 No 
               
               
                 K550R 
                 0.05 
                 0.03 
                 0.18 
                 0.03 
                 0.17 
                 0.07 
                 Yes 
                 Yes 
               
               
                 K550A 
                 −0.24 
                 0.04 
                 −0.06 
                 0.04 
                 −0.91 
                 0.13 
                 No 
                 No 
               
               
                 K550N 
                 0.11 
                 0.07 
                 −0.13 
                 0.07 
                 −0.46 
                 0.13 
                 Yes 
                 No 
               
               
                 K550D 
                 −0.86 
                 0.09 
                 0.22 
                 0.07 
                 −1.48 
                 0.23 
                 Yes 
                 No 
               
               
                 K550C 
                 −0.08 
                 0.07 
                 −0.18 
                 0.07 
                 −0.84 
                 0.21 
                 No 
                 No 
               
               
                 K550Q 
                 −0.18 
                 0.07 
                 0.45 
                 0.07 
                 −0.64 
                 0.18 
                 Yes 
                 No 
               
               
                 K550E 
                 −0.86 
                 0.06 
                 −0.45 
                 0.05 
                 −1.11 
                 0.09 
                 No 
                 No 
               
               
                 K550G 
                 −0.25 
                 0.02 
                 −0.16 
                 0.02 
                 −1.14 
                 0.04 
                 No 
                 No 
               
               
                 K550H 
                 −0.22 
                 0.15 
                 −0.42 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K550I 
                 −0.51 
                 0.12 
                 0.79 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K550L 
                 0.01 
                 0.05 
                 −0.17 
                 0.05 
                 −0.95 
                 0.06 
                 Yes 
                 No 
               
               
                 K550M 
                 −0.71 
                 0.08 
                 −0.17 
                 0.07 
                 −0.72 
                 0.15 
                 No 
                 No 
               
               
                 K550F 
                 −0.14 
                 0.10 
                 −0.39 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K550P 
                 −0.02 
                 0.08 
                 −0.78 
                 0.10 
                 −0.95 
                 0.27 
                 No 
                 No 
               
               
                 K550S 
                 −0.07 
                 0.05 
                 −0.22 
                 0.05 
                 −1.05 
                 0.08 
                 No 
                 No 
               
               
                 K550* 
                 −0.98 
                 0.08 
                 −1.14 
                 0.09 
                 −1.19 
                 0.10 
                 No 
                 No 
               
               
                 K550T 
                 −0.13 
                 0.06 
                 −0.44 
                 0.07 
                 −0.87 
                 0.14 
                 No 
                 No 
               
               
                 K550W 
                 0.18 
                 0.04 
                 0.20 
                 0.04 
                 −0.66 
                 0.07 
                 Yes 
                 No 
               
               
                 K550Y 
                 −0.12 
                 0.11 
                 −0.58 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K550V 
                 −0.12 
                 0.04 
                 −0.70 
                 0.05 
                 −1.02 
                 0.13 
                 No 
                 No 
               
               
                 N551D 
                 0.14 
                 0.04 
                 0.15 
                 0.04 
                 0.67 
                 0.07 
                 Yes 
                 Yes 
               
               
                 N551A 
                 −0.29 
                 0.04 
                 −0.42 
                 0.04 
                 −0.37 
                 0.05 
                 No 
                 No 
               
               
                 N551R 
                 −0.92 
                 0.04 
                 −1.40 
                 0.05 
                 −1.64 
                 0.09 
                 No 
                 No 
               
               
                 N551C 
                 −0.52 
                 0.08 
                 −0.26 
                 0.08 
                 −0.39 
                 0.28 
                 No 
                 No 
               
               
                 N551Q 
                 −0.77 
                 0.09 
                 −0.58 
                 0.08 
                 −0.76 
                 0.10 
                 No 
                 No 
               
               
                 N551E 
                 −1.32 
                 0.06 
                 −0.66 
                 0.05 
                 −1.51 
                 0.10 
                 No 
                 No 
               
               
                 N551G 
                 −0.95 
                 0.03 
                 −0.96 
                 0.03 
                 −1.10 
                 0.04 
                 No 
                 No 
               
               
                 N551H 
                 0.51 
                 0.09 
                 −1.02 
                 0.14 
                 0.55 
                 0.13 
                 Yes 
                 No 
               
               
                 N551I 
                 −0.01 
                 0.05 
                 0.20 
                 0.05 
                 −0.18 
                 0.11 
                 Yes 
                 No 
               
               
                 N551L 
                 −0.07 
                 0.05 
                 −0.83 
                 0.06 
                 −1.35 
                 0.11 
                 No 
                 No 
               
               
                 N551K 
                 −1.43 
                 0.07 
                 −1.28 
                 0.07 
                 −1.22 
                 0.08 
                 No 
                 No 
               
               
                 N551M 
                 −1.01 
                 0.09 
                 −0.58 
                 0.08 
                 −0.94 
                 0.18 
                 No 
                 No 
               
               
                 N551F 
                 −0.65 
                 0.11 
                 −0.19 
                 0.09 
                 −0.04 
                 0.24 
                 No 
                 No 
               
               
                 N551P 
                 −1.24 
                 0.10 
                 −0.91 
                 0.09 
                 −1.21 
                 0.12 
                 No 
                 No 
               
               
                 N551S 
                 −0.06 
                 0.03 
                 0.02 
                 0.03 
                 −0.23 
                 0.05 
                 Yes 
                 No 
               
               
                 N551* 
                 −1.09 
                 0.10 
                 −1.44 
                 0.11 
                 −1.45 
                 0.20 
                 No 
                 No 
               
               
                 N551T 
                 0.21 
                 0.05 
                 −0.29 
                 0.06 
                 0.07 
                 0.11 
                 Yes 
                 No 
               
               
                 N551W 
                 −0.36 
                 0.06 
                 −0.69 
                 0.06 
                 −0.63 
                 0.13 
                 No 
                 No 
               
               
                 N551Y 
                 −0.28 
                 0.07 
                 0.04 
                 0.06 
                 0.95 
                 0.10 
                 Yes 
                 No 
               
               
                 N551V 
                 −0.31 
                 0.04 
                 −0.21 
                 0.04 
                 0.03 
                 0.05 
                 Yes 
                 No 
               
               
                 N552A 
                 −1.33 
                 0.07 
                 −1.21 
                 0.07 
                 −1.32 
                 0.08 
                 No 
                 No 
               
               
                 N552R 
                 −1.19 
                 0.04 
                 −1.37 
                 0.05 
                 −1.47 
                 0.04 
                 No 
                 No 
               
               
                 N552D 
                 −1.18 
                 0.07 
                 −1.04 
                 0.06 
                 −1.24 
                 0.06 
                 No 
                 No 
               
               
                 N552C 
                 −1.59 
                 0.10 
                 −1.44 
                 0.09 
                 −1.65 
                 0.17 
                 No 
                 No 
               
               
                 N552Q 
                 −1.21 
                 0.11 
                 −0.81 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N552E 
                 −1.93 
                 0.09 
                 −0.57 
                 0.05 
                 −1.89 
                 0.06 
                 No 
                 No 
               
               
                 N552G 
                 −1.80 
                 0.05 
                 −1.17 
                 0.04 
                 −2.06 
                 0.03 
                 No 
                 No 
               
               
                 N552H 
                 −0.25 
                 0.10 
                 −0.21 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N552I 
                 −0.34 
                 0.05 
                 −0.02 
                 0.05 
                 −0.50 
                 0.09 
                 No 
                 No 
               
               
                 N552L 
                 −1.13 
                 0.07 
                 −1.91 
                 0.10 
                 −1.73 
                 0.12 
                 No 
                 No 
               
               
                 N552K 
                 −1.34 
                 0.08 
                 −1.25 
                 0.08 
                 −1.07 
                 0.10 
                 No 
                 No 
               
               
                 N552M 
                 −1.92 
                 0.12 
                 −1.44 
                 0.10 
                 −1.67 
                 0.11 
                 No 
                 No 
               
               
                 N552P 
                 −1.69 
                 0.12 
                 −0.81 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N552S 
                 −0.11 
                 0.03 
                 −0.20 
                 0.03 
                 −0.58 
                 0.05 
                 No 
                 No 
               
               
                 N552* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.37 
                 0.20 
                 Yes 
                 No 
               
               
                 N552T 
                 −0.16 
                 0.03 
                 0.00 
                 0.03 
                 −1.04 
                 0.10 
                 No 
                 No 
               
               
                 N552W 
                 −1.97 
                 0.10 
                 −1.69 
                 0.08 
                 −1.53 
                 0.15 
                 No 
                 No 
               
               
                 N552Y 
                 −0.89 
                 0.10 
                 −0.99 
                 0.10 
                 −1.08 
                 0.18 
                 No 
                 No 
               
               
                 N552V 
                 −1.60 
                 0.07 
                 −1.17 
                 0.06 
                 −1.56 
                 0.05 
                 No 
                 No 
               
               
                 G553A 
                 −0.56 
                 0.05 
                 −0.61 
                 0.05 
                 −1.53 
                 0.11 
                 No 
                 No 
               
               
                 G553R 
                 −1.58 
                 0.06 
                 −1.17 
                 0.05 
                 −0.39 
                 0.07 
                 No 
                 No 
               
               
                 G553D 
                 −0.48 
                 0.08 
                 −0.91 
                 0.09 
                 −0.94 
                 0.19 
                 No 
                 No 
               
               
                 G553Q 
                 −1.38 
                 0.15 
                 −1.10 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G553E 
                 −2.07 
                 0.11 
                 −1.79 
                 0.10 
                 −1.67 
                 0.17 
                 No 
                 No 
               
               
                 G553S 
                 −0.78 
                 0.06 
                 −0.54 
                 0.06 
                 −0.72 
                 0.09 
                 No 
                 No 
               
               
                 G553* 
                 −1.04 
                 0.12 
                 −1.39 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G553W 
                 −1.11 
                 0.07 
                 −1.87 
                 0.09 
                 −1.59 
                 0.16 
                 No 
                 No 
               
               
                 G553V 
                 −0.34 
                 0.03 
                 −0.24 
                 0.03 
                 −0.30 
                 0.05 
                 No 
                 No 
               
               
                 A554I 
                 0.15 
                 0.09 
                 0.71 
                 0.08 
                 0.39 
                 0.34 
                 Yes 
                 Yes 
               
               
                 A554T 
                 0.45 
                 0.04 
                 0.32 
                 0.05 
                 0.93 
                 0.07 
                 Yes 
                 Yes 
               
               
                 A554V 
                 0.57 
                 0.03 
                 0.48 
                 0.03 
                 0.54 
                 0.04 
                 Yes 
                 Yes 
               
               
                 A554R 
                 −1.28 
                 0.05 
                 −1.12 
                 0.05 
                 −2.05 
                 0.11 
                 No 
                 No 
               
               
                 A554N 
                 0.04 
                 0.09 
                 −0.71 
                 0.11 
                 −0.12 
                 0.13 
                 Yes 
                 No 
               
               
                 A554D 
                 −1.96 
                 0.10 
                 −0.95 
                 0.07 
                 −0.83 
                 0.04 
                 No 
                 No 
               
               
                 A554C 
                 −0.05 
                 0.07 
                 0.32 
                 0.06 
                 1.05 
                 0.09 
                 Yes 
                 No 
               
               
                 A554Q 
                 −0.47 
                 0.10 
                 −0.57 
                 0.10 
                 −1.06 
                 0.28 
                 No 
                 No 
               
               
                 A554E 
                 −1.85 
                 0.09 
                 −0.79 
                 0.06 
                 −1.86 
                 0.11 
                 No 
                 No 
               
               
                 A554G 
                 −0.43 
                 0.03 
                 −0.54 
                 0.03 
                 −0.70 
                 0.04 
                 No 
                 No 
               
               
                 A554L 
                 −0.23 
                 0.05 
                 −0.11 
                 0.05 
                 −0.32 
                 0.17 
                 No 
                 No 
               
               
                 A554M 
                 0.27 
                 0.07 
                 −0.26 
                 0.08 
                 −0.72 
                 0.23 
                 Yes 
                 No 
               
               
                 A554P 
                 −1.28 
                 0.09 
                 −1.84 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A554S 
                 0.14 
                 0.03 
                 0.15 
                 0.03 
                 −0.07 
                 0.05 
                 Yes 
                 No 
               
               
                 A554* 
                 −1.77 
                 0.14 
                 −1.03 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A554W 
                 −1.54 
                 0.09 
                 −2.63 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I555V 
                 0.41 
                 0.03 
                 0.13 
                 0.03 
                 0.14 
                 0.06 
                 Yes 
                 Yes 
               
               
                 I555A 
                 −0.39 
                 0.05 
                 −0.48 
                 0.05 
                 −0.79 
                 0.14 
                 No 
                 No 
               
               
                 I555R 
                 −0.47 
                 0.04 
                 −1.21 
                 0.05 
                 −0.58 
                 0.09 
                 No 
                 No 
               
               
                 I555N 
                 −0.51 
                 0.08 
                 −0.76 
                 0.08 
                 −0.76 
                 0.13 
                 No 
                 No 
               
               
                 I555D 
                 −1.00 
                 0.09 
                 −1.17 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I555C 
                 −1.00 
                 0.12 
                 −0.93 
                 0.12 
                 −0.75 
                 0.10 
                 No 
                 No 
               
               
                 I555Q 
                 −0.79 
                 0.11 
                 −0.92 
                 0.11 
                 −0.84 
                 0.21 
                 No 
                 No 
               
               
                 I555E 
                 −2.31 
                 0.12 
                 −0.09 
                 0.05 
                 −1.79 
                 0.15 
                 No 
                 No 
               
               
                 I555G 
                 −1.15 
                 0.04 
                 −1.07 
                 0.04 
                 −1.57 
                 0.03 
                 No 
                 No 
               
               
                 I555L 
                 0.18 
                 0.05 
                 −0.03 
                 0.05 
                 −0.30 
                 0.14 
                 Yes 
                 No 
               
               
                 I555K 
                 −0.71 
                 0.09 
                 −0.03 
                 0.07 
                 −1.33 
                 0.11 
                 No 
                 No 
               
               
                 I555M 
                 −0.04 
                 0.05 
                 −0.01 
                 0.05 
                 −0.27 
                 0.08 
                 No 
                 No 
               
               
                 I555F 
                 −0.18 
                 0.09 
                 −0.17 
                 0.09 
                 −0.32 
                 0.13 
                 No 
                 No 
               
               
                 I555P 
                 −1.29 
                 0.11 
                 −1.66 
                 0.13 
                 −1.11 
                 0.36 
                 No 
                 No 
               
               
                 I555S 
                 −0.16 
                 0.03 
                 −0.12 
                 0.03 
                 −0.31 
                 0.05 
                 No 
                 No 
               
               
                 I555T 
                 −0.01 
                 0.05 
                 −0.09 
                 0.05 
                 −0.45 
                 0.11 
                 No 
                 No 
               
               
                 I555W 
                 −1.78 
                 0.11 
                 −1.29 
                 0.09 
                 −1.81 
                 0.15 
                 No 
                 No 
               
               
                 I555Y 
                 −1.05 
                 0.14 
                 −1.16 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556M 
                 0.08 
                 0.08 
                 0.10 
                 0.08 
                 0.11 
                 0.21 
                 Yes 
                 Yes 
               
               
                 L556A 
                 −0.52 
                 0.07 
                 −1.77 
                 0.12 
                 −1.33 
                 0.24 
                 No 
                 No 
               
               
                 L556R 
                 −1.06 
                 0.06 
                 −0.91 
                 0.06 
                 −1.39 
                 0.10 
                 No 
                 No 
               
               
                 L556C 
                 −1.31 
                 0.13 
                 −0.58 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556Q 
                 −0.06 
                 0.06 
                 −0.34 
                 0.07 
                 −0.36 
                 0.11 
                 No 
                 No 
               
               
                 L556G 
                 −1.55 
                 0.07 
                 −1.49 
                 0.07 
                 −1.60 
                 0.06 
                 No 
                 No 
               
               
                 L556I 
                 0.58 
                 0.12 
                 0.07 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556P 
                 −0.19 
                 0.07 
                 −0.54 
                 0.08 
                 −0.91 
                 0.13 
                 No 
                 No 
               
               
                 L556S 
                 −1.56 
                 0.11 
                 −1.28 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556T 
                 −0.95 
                 0.12 
                 −0.69 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556W 
                 −1.77 
                 0.12 
                 −1.41 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L556V 
                 −0.45 
                 0.06 
                 −0.17 
                 0.05 
                 −0.76 
                 0.14 
                 No 
                 No 
               
               
                 F557A 
                 −0.39 
                 0.05 
                 −0.06 
                 0.05 
                 −0.75 
                 0.07 
                 No 
                 No 
               
               
                 F557R 
                 −1.79 
                 0.06 
                 −1.05 
                 0.05 
                 −1.57 
                 0.08 
                 No 
                 No 
               
               
                 F557N 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.90 
                 0.11 
                 Yes 
                 No 
               
               
                 F557C 
                 −0.63 
                 0.06 
                 −0.55 
                 0.06 
                 −0.32 
                 0.13 
                 No 
                 No 
               
               
                 F557Q 
                 −1.87 
                 0.15 
                 −0.40 
                 0.09 
                 −0.98 
                 0.25 
                 No 
                 No 
               
               
                 F557E 
                 −1.90 
                 0.10 
                 −1.64 
                 0.09 
                 −1.50 
                 0.16 
                 No 
                 No 
               
               
                 F557G 
                 −1.17 
                 0.04 
                 −1.02 
                 0.04 
                 −0.98 
                 0.06 
                 No 
                 No 
               
               
                 F557I 
                 −0.32 
                 0.05 
                 −0.07 
                 0.04 
                 −0.05 
                 0.08 
                 No 
                 No 
               
               
                 F557L 
                 −0.04 
                 0.04 
                 −0.08 
                 0.04 
                 0.14 
                 0.08 
                 Yes 
                 No 
               
               
                 F557K 
                 −1.25 
                 0.10 
                 −0.84 
                 0.09 
                 −0.79 
                 0.30 
                 No 
                 No 
               
               
                 F557M 
                 0.33 
                 0.07 
                 −0.19 
                 0.08 
                 −0.15 
                 0.18 
                 Yes 
                 No 
               
               
                 F557P 
                 −1.14 
                 0.10 
                 −1.38 
                 0.11 
                 −1.69 
                 0.21 
                 No 
                 No 
               
               
                 F557S 
                 −0.87 
                 0.05 
                 −0.74 
                 0.05 
                 −0.48 
                 0.09 
                 No 
                 No 
               
               
                 F557* 
                 −1.30 
                 0.10 
                 −2.32 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F557T 
                 −1.21 
                 0.09 
                 −0.72 
                 0.08 
                 −0.44 
                 0.25 
                 No 
                 No 
               
               
                 F557W 
                 −0.87 
                 0.06 
                 −0.37 
                 0.05 
                 −1.24 
                 0.11 
                 No 
                 No 
               
               
                 F557Y 
                 −0.74 
                 0.08 
                 −0.15 
                 0.07 
                 −0.87 
                 0.13 
                 No 
                 No 
               
               
                 F557V 
                 −0.50 
                 0.04 
                 −0.91 
                 0.05 
                 −0.42 
                 0.04 
                 No 
                 No 
               
               
                 V558M 
                 0.24 
                 0.06 
                 0.15 
                 0.06 
                 0.10 
                 0.12 
                 Yes 
                 Yes 
               
               
                 V558A 
                 −0.11 
                 0.04 
                 −0.13 
                 0.04 
                 0.26 
                 0.09 
                 Yes 
                 No 
               
               
                 V558R 
                 −0.63 
                 0.06 
                 −0.46 
                 0.05 
                 −0.26 
                 0.14 
                 No 
                 No 
               
               
                 V558D 
                 0.64 
                 0.09 
                 0.05 
                 0.10 
                 −0.46 
                 0.14 
                 Yes 
                 No 
               
               
                 V558C 
                 −0.01 
                 0.12 
                 0.01 
                 0.12 
                 −0.28 
                 0.55 
                 Yes 
                 No 
               
               
                 V558Q 
                 0.40 
                 0.11 
                 −0.65 
                 0.14 
                 −0.21 
                 0.55 
                 Yes 
                 No 
               
               
                 V558E 
                 0.15 
                 0.04 
                 −0.31 
                 0.05 
                 −0.12 
                 0.07 
                 Yes 
                 No 
               
               
                 V558G 
                 −0.07 
                 0.03 
                 −0.48 
                 0.04 
                 −0.36 
                 0.10 
                 No 
                 No 
               
               
                 V558L 
                 0.16 
                 0.04 
                 0.03 
                 0.04 
                 −0.16 
                 0.09 
                 Yes 
                 No 
               
               
                 V558K 
                 0.05 
                 0.10 
                 −0.15 
                 0.11 
                 −0.02 
                 0.48 
                 Yes 
                 No 
               
               
                 V558F 
                 −0.21 
                 0.13 
                 −0.36 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V558S 
                 −0.36 
                 0.09 
                 −0.49 
                 0.09 
                 −0.10 
                 0.27 
                 No 
                 No 
               
               
                 V558T 
                 −0.19 
                 0.12 
                 −0.28 
                 0.12 
                 0.15 
                 0.41 
                 Yes 
                 No 
               
               
                 V558W 
                 −0.76 
                 0.10 
                 −0.75 
                 0.10 
                 −0.93 
                 0.30 
                 No 
                 No 
               
               
                 K559A 
                 0.17 
                 0.04 
                 0.08 
                 0.04 
                 0.13 
                 0.08 
                 Yes 
                 Yes 
               
               
                 K559R 
                 0.14 
                 0.03 
                 −0.02 
                 0.03 
                 0.11 
                 0.06 
                 Yes 
                 No 
               
               
                 K559N 
                 0.05 
                 0.03 
                 0.05 
                 0.03 
                 −0.04 
                 0.05 
                 Yes 
                 No 
               
               
                 K559D 
                 0.25 
                 0.08 
                 −0.33 
                 0.09 
                 −0.39 
                 0.25 
                 Yes 
                 No 
               
               
                 K559C 
                 0.31 
                 0.08 
                 −0.20 
                 0.09 
                 −0.05 
                 0.22 
                 Yes 
                 No 
               
               
                 K559Q 
                 −0.23 
                 0.07 
                 0.03 
                 0.07 
                 0.00 
                 0.21 
                 Yes 
                 No 
               
               
                 K559E 
                 −0.20 
                 0.04 
                 −0.52 
                 0.04 
                 −0.40 
                 0.06 
                 No 
                 No 
               
               
                 K559G 
                 −0.35 
                 0.03 
                 −0.41 
                 0.03 
                 −0.16 
                 0.03 
                 No 
                 No 
               
               
                 K559H 
                 0.53 
                 0.14 
                 −0.21 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K559I 
                 −0.62 
                 0.12 
                 0.01 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K559L 
                 −0.39 
                 0.06 
                 −0.29 
                 0.06 
                 −0.71 
                 0.13 
                 No 
                 No 
               
               
                 K559M 
                 −0.27 
                 0.06 
                 −0.65 
                 0.07 
                 0.01 
                 0.12 
                 Yes 
                 No 
               
               
                 K559F 
                 −0.45 
                 0.13 
                 0.13 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K559S 
                 −0.28 
                 0.06 
                 −0.32 
                 0.06 
                 0.22 
                 0.20 
                 Yes 
                 No 
               
               
                 K559* 
                 −0.63 
                 0.07 
                 −0.48 
                 0.07 
                 −1.15 
                 0.09 
                 No 
                 No 
               
               
                 K559T 
                 0.30 
                 0.06 
                 0.52 
                 0.06 
                 −0.20 
                 0.15 
                 Yes 
                 No 
               
               
                 K559W 
                 −0.64 
                 0.06 
                 −0.34 
                 0.06 
                 −0.32 
                 0.18 
                 No 
                 No 
               
               
                 K559Y 
                 −0.13 
                 0.11 
                 −0.01 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K559V 
                 −0.53 
                 0.05 
                 −0.50 
                 0.05 
                 −0.27 
                 0.13 
                 No 
                 No 
               
               
                 N560A 
                 0.34 
                 0.05 
                 0.18 
                 0.05 
                 0.18 
                 0.08 
                 Yes 
                 Yes 
               
               
                 N560D 
                 0.16 
                 0.04 
                 0.18 
                 0.04 
                 0.16 
                 0.08 
                 Yes 
                 Yes 
               
               
                 N560E 
                 0.48 
                 0.06 
                 0.28 
                 0.06 
                 0.11 
                 0.25 
                 Yes 
                 Yes 
               
               
                 N560M 
                 0.16 
                 0.09 
                 0.31 
                 0.09 
                 0.18 
                 0.13 
                 Yes 
                 Yes 
               
               
                 N560R 
                 0.10 
                 0.04 
                 0.04 
                 0.04 
                 −0.07 
                 0.06 
                 Yes 
                 No 
               
               
                 N560C 
                 −0.11 
                 0.08 
                 −0.20 
                 0.08 
                 −0.15 
                 0.09 
                 No 
                 No 
               
               
                 N560Q 
                 0.55 
                 0.09 
                 −1.07 
                 0.14 
                 −0.09 
                 0.38 
                 Yes 
                 No 
               
               
                 N560G 
                 0.01 
                 0.04 
                 0.03 
                 0.04 
                 −0.02 
                 0.09 
                 Yes 
                 No 
               
               
                 N560H 
                 −0.35 
                 0.13 
                 −0.17 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N560I 
                 0.22 
                 0.05 
                 0.28 
                 0.05 
                 −0.13 
                 0.10 
                 Yes 
                 No 
               
               
                 N560L 
                 −0.64 
                 0.08 
                 −0.16 
                 0.07 
                 −0.12 
                 0.11 
                 No 
                 No 
               
               
                 N560K 
                 0.11 
                 0.06 
                 −0.29 
                 0.07 
                 0.14 
                 0.14 
                 Yes 
                 No 
               
               
                 N560F 
                 0.14 
                 0.12 
                 −0.03 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N560P 
                 0.19 
                 0.09 
                 −0.69 
                 0.11 
                 −0.13 
                 0.29 
                 Yes 
                 No 
               
               
                 N560S 
                 0.03 
                 0.03 
                 0.18 
                 0.03 
                 −0.01 
                 0.05 
                 Yes 
                 No 
               
               
                 N560* 
                 −1.15 
                 0.11 
                 −1.78 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N560T 
                 −0.40 
                 0.08 
                 0.00 
                 0.07 
                 0.01 
                 0.14 
                 Yes 
                 No 
               
               
                 N560W 
                 −0.36 
                 0.07 
                 −0.72 
                 0.08 
                 −0.27 
                 0.16 
                 No 
                 No 
               
               
                 N560Y 
                 −0.24 
                 0.09 
                 0.04 
                 0.08 
                 0.07 
                 0.12 
                 Yes 
                 No 
               
               
                 N560V 
                 0.13 
                 0.06 
                 −0.15 
                 0.06 
                 −0.11 
                 0.16 
                 Yes 
                 No 
               
               
                 G561A 
                 −0.10 
                 0.05 
                 −0.36 
                 0.06 
                 −0.05 
                 0.07 
                 No 
                 No 
               
               
                 G561R 
                 −0.20 
                 0.04 
                 0.00 
                 0.04 
                 −0.16 
                 0.05 
                 No 
                 No 
               
               
                 G561N 
                 0.20 
                 0.16 
                 1.09 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G561D 
                 −0.43 
                 0.11 
                 0.54 
                 0.08 
                 −0.03 
                 0.27 
                 Yes 
                 No 
               
               
                 G561C 
                 −0.19 
                 0.08 
                 0.03 
                 0.08 
                 −0.26 
                 0.27 
                 Yes 
                 No 
               
               
                 G561Q 
                 −0.15 
                 0.12 
                 0.67 
                 0.10 
                 −0.08 
                 0.26 
                 Yes 
                 No 
               
               
                 G561E 
                 0.14 
                 0.06 
                 −0.19 
                 0.06 
                 −0.05 
                 0.14 
                 Yes 
                 No 
               
               
                 G561H 
                 0.74 
                 0.14 
                 1.07 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G561L 
                 −0.57 
                 0.09 
                 −0.30 
                 0.09 
                 −0.60 
                 0.09 
                 No 
                 No 
               
               
                 G561K 
                 0.24 
                 0.12 
                 0.17 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G561M 
                 −0.33 
                 0.14 
                 0.12 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G561P 
                 −0.84 
                 0.12 
                 −0.45 
                 0.11 
                 0.02 
                 0.17 
                 Yes 
                 No 
               
               
                 G561S 
                 0.00 
                 0.06 
                 0.54 
                 0.05 
                 −0.09 
                 0.18 
                 Yes 
                 No 
               
               
                 G561* 
                 −0.53 
                 0.11 
                 −0.01 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G561T 
                 0.10 
                 0.09 
                 −0.87 
                 0.13 
                 −0.23 
                 0.34 
                 Yes 
                 No 
               
               
                 G561W 
                 −0.47 
                 0.06 
                 −0.34 
                 0.06 
                 −0.51 
                 0.17 
                 No 
                 No 
               
               
                 G561V 
                 −0.02 
                 0.02 
                 −0.04 
                 0.02 
                 0.08 
                 0.06 
                 Yes 
                 No 
               
               
                 L562A 
                 −0.46 
                 0.07 
                 −0.26 
                 0.07 
                 −0.17 
                 0.22 
                 No 
                 No 
               
               
                 L562R 
                 −0.38 
                 0.05 
                 0.08 
                 0.04 
                 −0.17 
                 0.08 
                 Yes 
                 No 
               
               
                 L562D 
                 −0.37 
                 0.13 
                 −0.90 
                 0.15 
                 −0.46 
                 0.35 
                 No 
                 No 
               
               
                 L562C 
                 0.18 
                 0.10 
                 −0.63 
                 0.12 
                 0.13 
                 0.29 
                 Yes 
                 No 
               
               
                 L562Q 
                 −0.43 
                 0.09 
                 −0.20 
                 0.08 
                 −0.07 
                 0.17 
                 No 
                 No 
               
               
                 L562E 
                 −0.32 
                 0.07 
                 −0.62 
                 0.08 
                 −0.29 
                 0.18 
                 No 
                 No 
               
               
                 L562G 
                 −0.75 
                 0.05 
                 −0.60 
                 0.05 
                 −0.36 
                 0.08 
                 No 
                 No 
               
               
                 L562H 
                 0.23 
                 0.12 
                 −0.50 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L562K 
                 −0.69 
                 0.12 
                 0.32 
                 0.09 
                 −0.53 
                 0.29 
                 Yes 
                 No 
               
               
                 L562M 
                 0.19 
                 0.06 
                 −0.26 
                 0.07 
                 −0.04 
                 0.12 
                 Yes 
                 No 
               
               
                 L562F 
                 0.48 
                 0.14 
                 0.79 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L562P 
                 −0.10 
                 0.06 
                 −0.05 
                 0.06 
                 −0.26 
                 0.09 
                 No 
                 No 
               
               
                 L562S 
                 −0.65 
                 0.10 
                 −0.27 
                 0.09 
                 −0.04 
                 0.26 
                 No 
                 No 
               
               
                 L562* 
                 −1.29 
                 0.14 
                 −1.10 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L562T 
                 −1.14 
                 0.15 
                 −1.09 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L562W 
                 −0.37 
                 0.07 
                 −0.38 
                 0.07 
                 −0.45 
                 0.18 
                 No 
                 No 
               
               
                 L562Y 
                 −0.63 
                 0.16 
                 −0.49 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L562V 
                 −0.20 
                 0.05 
                 −0.49 
                 0.06 
                 −0.71 
                 0.11 
                 No 
                 No 
               
               
                 Y563A 
                 −1.58 
                 0.09 
                 −1.18 
                 0.08 
                 −1.03 
                 0.07 
                 No 
                 No 
               
               
                 Y563R 
                 −1.46 
                 0.06 
                 −1.08 
                 0.05 
                 −1.59 
                 0.11 
                 No 
                 No 
               
               
                 Y563N 
                 −0.16 
                 0.08 
                 0.04 
                 0.07 
                 −0.30 
                 0.16 
                 Yes 
                 No 
               
               
                 Y563D 
                 −0.56 
                 0.07 
                 −0.65 
                 0.07 
                 −0.73 
                 0.07 
                 No 
                 No 
               
               
                 Y563C 
                 −0.49 
                 0.06 
                 −0.50 
                 0.06 
                 −0.32 
                 0.09 
                 No 
                 No 
               
               
                 Y563Q 
                 −0.48 
                 0.10 
                 −0.52 
                 0.10 
                 −0.93 
                 0.25 
                 No 
                 No 
               
               
                 Y563E 
                 −1.21 
                 0.08 
                 0.07 
                 0.06 
                 −1.73 
                 0.14 
                 Yes 
                 No 
               
               
                 Y563G 
                 −1.13 
                 0.04 
                 −1.64 
                 0.05 
                 −1.26 
                 0.03 
                 No 
                 No 
               
               
                 Y563H 
                 −0.25 
                 0.08 
                 −0.14 
                 0.08 
                 −0.06 
                 0.15 
                 No 
                 No 
               
               
                 Y563L 
                 −1.95 
                 0.12 
                 −1.69 
                 0.11 
                 −1.15 
                 0.19 
                 No 
                 No 
               
               
                 Y563F 
                 0.13 
                 0.07 
                 0.06 
                 0.07 
                 −0.06 
                 0.11 
                 Yes 
                 No 
               
               
                 Y563S 
                 −0.91 
                 0.07 
                 −0.95 
                 0.07 
                 −0.96 
                 0.08 
                 No 
                 No 
               
               
                 Y563* 
                 −0.54 
                 0.08 
                 −0.93 
                 0.09 
                 −1.33 
                 0.14 
                 No 
                 No 
               
               
                 Y563T 
                 −1.67 
                 0.15 
                 0.09 
                 0.08 
                 −0.51 
                 0.22 
                 Yes 
                 No 
               
               
                 Y563W 
                 −0.84 
                 0.06 
                 −0.78 
                 0.05 
                 −1.12 
                 0.11 
                 No 
                 No 
               
               
                 Y563V 
                 −1.32 
                 0.08 
                 −1.12 
                 0.07 
                 −1.13 
                 0.17 
                 No 
                 No 
               
               
                 Y564A 
                 −1.20 
                 0.15 
                 −0.93 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y564R 
                 −1.37 
                 0.10 
                 −1.99 
                 0.13 
                 −1.19 
                 0.19 
                 No 
                 No 
               
               
                 Y564N 
                 −0.18 
                 0.12 
                 0.08 
                 0.11 
                 −0.14 
                 0.21 
                 Yes 
                 No 
               
               
                 Y564D 
                 −0.05 
                 0.06 
                 −0.60 
                 0.07 
                 −0.25 
                 0.10 
                 No 
                 No 
               
               
                 Y564C 
                 0.09 
                 0.05 
                 −0.22 
                 0.05 
                 −0.08 
                 0.10 
                 Yes 
                 No 
               
               
                 Y564G 
                 −1.96 
                 0.11 
                 −1.74 
                 0.10 
                 −1.32 
                 0.19 
                 No 
                 No 
               
               
                 Y564H 
                 −0.05 
                 0.08 
                 −0.10 
                 0.08 
                 0.04 
                 0.13 
                 Yes 
                 No 
               
               
                 Y564L 
                 −0.24 
                 0.10 
                 −1.01 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y564F 
                 −0.04 
                 0.11 
                 0.35 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y564S 
                 −0.47 
                 0.09 
                 −0.36 
                 0.08 
                 −0.35 
                 0.20 
                 No 
                 No 
               
               
                 Y564* 
                 −0.43 
                 0.11 
                 −0.68 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y564W 
                 −0.37 
                 0.10 
                 0.03 
                 0.09 
                 −0.52 
                 0.29 
                 Yes 
                 No 
               
               
                 Y564V 
                 −1.90 
                 0.15 
                 −0.72 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L565A 
                 −0.65 
                 0.07 
                 −0.47 
                 0.06 
                 −1.27 
                 0.23 
                 No 
                 No 
               
               
                 L565R 
                 −0.27 
                 0.03 
                 −0.79 
                 0.03 
                 −0.12 
                 0.05 
                 No 
                 No 
               
               
                 L565C 
                 −1.21 
                 0.13 
                 −0.10 
                 0.09 
                 −0.66 
                 0.24 
                 No 
                 No 
               
               
                 L565Q 
                 −0.36 
                 0.08 
                 −0.84 
                 0.09 
                 −0.76 
                 0.15 
                 No 
                 No 
               
               
                 L565E 
                 −1.93 
                 0.12 
                 −1.02 
                 0.09 
                 −1.55 
                 0.19 
                 No 
                 No 
               
               
                 L565G 
                 −2.36 
                 0.08 
                 −1.62 
                 0.06 
                 −1.50 
                 0.10 
                 No 
                 No 
               
               
                 L565I 
                 −0.07 
                 0.13 
                 −0.42 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L565M 
                 −0.20 
                 0.07 
                 −0.26 
                 0.07 
                 0.03 
                 0.10 
                 Yes 
                 No 
               
               
                 L565P 
                 −0.60 
                 0.07 
                 −0.92 
                 0.08 
                 −0.67 
                 0.13 
                 No 
                 No 
               
               
                 L565S 
                 −1.07 
                 0.09 
                 −0.75 
                 0.08 
                 −1.13 
                 0.08 
                 No 
                 No 
               
               
                 L565W 
                 −1.64 
                 0.10 
                 −2.31 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L565V 
                 −0.57 
                 0.06 
                 −0.48 
                 0.05 
                 −1.19 
                 0.13 
                 No 
                 No 
               
               
                 G566A 
                 −0.36 
                 0.08 
                 −0.39 
                 0.08 
                 −0.57 
                 0.21 
                 No 
                 No 
               
               
                 G566R 
                 −1.37 
                 0.09 
                 −1.97 
                 0.12 
                 −1.83 
                 0.11 
                 No 
                 No 
               
               
                 G566D 
                 −0.67 
                 0.11 
                 −1.03 
                 0.12 
                 −0.62 
                 0.18 
                 No 
                 No 
               
               
                 G566C 
                 −0.08 
                 0.11 
                 −0.83 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G566S 
                 −0.14 
                 0.06 
                 −0.40 
                 0.07 
                 −0.18 
                 0.11 
                 No 
                 No 
               
               
                 G566V 
                 −0.52 
                 0.07 
                 −0.99 
                 0.08 
                 −0.68 
                 0.10 
                 No 
                 No 
               
               
                 I567A 
                 −1.35 
                 0.11 
                 −1.01 
                 0.09 
                 −1.13 
                 0.07 
                 No 
                 No 
               
               
                 I567R 
                 −1.78 
                 0.09 
                 −0.11 
                 0.05 
                 −1.44 
                 0.11 
                 No 
                 No 
               
               
                 I567N 
                 −0.05 
                 0.07 
                 −0.10 
                 0.07 
                 0.15 
                 0.10 
                 Yes 
                 No 
               
               
                 I567E 
                 −1.64 
                 0.12 
                 −1.70 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I567G 
                 −1.23 
                 0.06 
                 −1.14 
                 0.06 
                 −1.70 
                 0.09 
                 No 
                 No 
               
               
                 I567L 
                 −0.67 
                 0.08 
                 0.29 
                 0.06 
                 −0.48 
                 0.13 
                 Yes 
                 No 
               
               
                 I567M 
                 −0.51 
                 0.09 
                 −0.82 
                 0.10 
                 −0.88 
                 0.10 
                 No 
                 No 
               
               
                 I567F 
                 −0.43 
                 0.12 
                 0.00 
                 0.11 
                 −0.48 
                 0.19 
                 No 
                 No 
               
               
                 I567S 
                 −0.56 
                 0.07 
                 −0.67 
                 0.07 
                 −0.82 
                 0.12 
                 No 
                 No 
               
               
                 I567T 
                 −0.15 
                 0.05 
                 −0.27 
                 0.06 
                 0.13 
                 0.09 
                 Yes 
                 No 
               
               
                 I567W 
                 −1.85 
                 0.12 
                 −2.17 
                 0.14 
                 −1.22 
                 0.13 
                 No 
                 No 
               
               
                 I567V 
                 −0.54 
                 0.05 
                 −0.26 
                 0.05 
                 −0.68 
                 0.08 
                 No 
                 No 
               
               
                 M568A 
                 −0.52 
                 0.06 
                 −0.34 
                 0.06 
                 −0.04 
                 0.11 
                 No 
                 No 
               
               
                 M568R 
                 −0.30 
                 0.04 
                 −0.82 
                 0.05 
                 −0.20 
                 0.07 
                 No 
                 No 
               
               
                 M568C 
                 −0.33 
                 0.10 
                 −0.78 
                 0.11 
                 −0.18 
                 0.28 
                 No 
                 No 
               
               
                 M568Q 
                 −0.61 
                 0.12 
                 −0.40 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M568E 
                 −1.29 
                 0.09 
                 −0.86 
                 0.08 
                 −1.65 
                 0.22 
                 No 
                 No 
               
               
                 M568G 
                 −1.32 
                 0.05 
                 −0.45 
                 0.04 
                 −0.80 
                 0.04 
                 No 
                 No 
               
               
                 M568H 
                 0.40 
                 0.14 
                 −0.11 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M568I 
                 0.16 
                 0.05 
                 −0.01 
                 0.06 
                 0.15 
                 0.11 
                 Yes 
                 No 
               
               
                 M568L 
                 −0.42 
                 0.06 
                 −0.23 
                 0.05 
                 −0.27 
                 0.09 
                 No 
                 No 
               
               
                 M568K 
                 −0.19 
                 0.08 
                 −0.20 
                 0.08 
                 −0.17 
                 0.16 
                 No 
                 No 
               
               
                 M568P 
                 −1.11 
                 0.13 
                 −0.81 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M568S 
                 0.29 
                 0.06 
                 −0.47 
                 0.07 
                 −0.54 
                 0.22 
                 Yes 
                 No 
               
               
                 M568T 
                 −0.13 
                 0.06 
                 −0.25 
                 0.06 
                 −0.07 
                 0.12 
                 No 
                 No 
               
               
                 M568W 
                 −0.20 
                 0.06 
                 0.14 
                 0.05 
                 −0.93 
                 0.18 
                 Yes 
                 No 
               
               
                 M568V 
                 −0.26 
                 0.04 
                 −0.28 
                 0.04 
                 0.06 
                 0.08 
                 Yes 
                 No 
               
               
                 P569D 
                 0.60 
                 0.08 
                 0.33 
                 0.08 
                 1.25 
                 0.11 
                 Yes 
                 Yes 
               
               
                 P569A 
                 −0.12 
                 0.05 
                 −0.39 
                 0.05 
                 0.23 
                 0.08 
                 Yes 
                 No 
               
               
                 P569R 
                 −0.60 
                 0.04 
                 −0.52 
                 0.04 
                 −0.13 
                 0.05 
                 No 
                 No 
               
               
                 P569N 
                 −0.14 
                 0.14 
                 −0.71 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P569C 
                 −1.16 
                 0.09 
                 −0.36 
                 0.07 
                 0.07 
                 0.19 
                 Yes 
                 No 
               
               
                 P569Q 
                 −0.26 
                 0.09 
                 −0.13 
                 0.09 
                 0.40 
                 0.21 
                 Yes 
                 No 
               
               
                 P569E 
                 −0.07 
                 0.07 
                 −0.16 
                 0.07 
                 −0.11 
                 0.22 
                 No 
                 No 
               
               
                 P569G 
                 −0.54 
                 0.03 
                 −0.49 
                 0.03 
                 −0.65 
                 0.07 
                 No 
                 No 
               
               
                 P569H 
                 0.12 
                 0.09 
                 −0.25 
                 0.10 
                 0.16 
                 0.17 
                 Yes 
                 No 
               
               
                 P569I 
                 0.03 
                 0.13 
                 −0.32 
                 0.14 
                 0.10 
                 0.31 
                 Yes 
                 No 
               
               
                 P569L 
                 −0.47 
                 0.05 
                 −0.21 
                 0.04 
                 −0.30 
                 0.11 
                 No 
                 No 
               
               
                 P569K 
                 −0.35 
                 0.12 
                 0.36 
                 0.10 
                 0.23 
                 0.31 
                 Yes 
                 No 
               
               
                 P569M 
                 −0.98 
                 0.11 
                 −0.54 
                 0.10 
                 −0.28 
                 0.12 
                 No 
                 No 
               
               
                 P569F 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.67 
                 0.31 
                 Yes 
                 No 
               
               
                 P569S 
                 −0.07 
                 0.05 
                 −0.24 
                 0.05 
                 0.02 
                 0.11 
                 Yes 
                 No 
               
               
                 P569T 
                 −0.38 
                 0.07 
                 −0.20 
                 0.07 
                 −0.06 
                 0.15 
                 No 
                 No 
               
               
                 P569W 
                 −0.74 
                 0.06 
                 −1.07 
                 0.07 
                 −1.18 
                 0.14 
                 No 
                 No 
               
               
                 P569V 
                 −0.34 
                 0.04 
                 −0.82 
                 0.05 
                 0.15 
                 0.14 
                 Yes 
                 No 
               
               
                 K570A 
                 −0.95 
                 0.06 
                 −0.28 
                 0.05 
                 −1.70 
                 0.16 
                 No 
                 No 
               
               
                 K570R 
                 −0.47 
                 0.03 
                 −0.56 
                 0.04 
                 −0.39 
                 0.05 
                 No 
                 No 
               
               
                 K570N 
                 −0.30 
                 0.11 
                 −0.73 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K570D 
                 −1.38 
                 0.12 
                 −1.42 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K570C 
                 −1.71 
                 0.11 
                 −1.70 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K570Q 
                 −0.90 
                 0.09 
                 −0.32 
                 0.08 
                 −1.25 
                 0.18 
                 No 
                 No 
               
               
                 K570E 
                 −1.37 
                 0.07 
                 −0.71 
                 0.05 
                 −1.40 
                 0.10 
                 No 
                 No 
               
               
                 K570G 
                 −0.62 
                 0.03 
                 −0.33 
                 0.03 
                 −1.61 
                 0.09 
                 No 
                 No 
               
               
                 K570L 
                 −1.83 
                 0.08 
                 −1.48 
                 0.07 
                 −1.35 
                 0.14 
                 No 
                 No 
               
               
                 K570M 
                 −1.02 
                 0.09 
                 −0.76 
                 0.09 
                 −1.52 
                 0.18 
                 No 
                 No 
               
               
                 K570P 
                 −1.15 
                 0.12 
                 −0.12 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K570S 
                 −1.28 
                 0.09 
                 −0.51 
                 0.07 
                 −1.52 
                 0.14 
                 No 
                 No 
               
               
                 K570* 
                 −1.31 
                 0.10 
                 −1.26 
                 0.10 
                 −1.24 
                 0.15 
                 No 
                 No 
               
               
                 K570T 
                 −0.02 
                 0.03 
                 0.11 
                 0.03 
                 −0.05 
                 0.03 
                 Yes 
                 No 
               
               
                 K570W 
                 −2.06 
                 0.09 
                 −2.64 
                 0.12 
                 −1.61 
                 0.14 
                 No 
                 No 
               
               
                 K570V 
                 −1.33 
                 0.06 
                 −0.81 
                 0.05 
                 −1.85 
                 0.11 
                 No 
                 No 
               
               
                 Q571A 
                 0.64 
                 0.07 
                 0.39 
                 0.08 
                 1.09 
                 0.23 
                 Yes 
                 Yes 
               
               
                 Q571P 
                 0.17 
                 0.07 
                 0.61 
                 0.07 
                 0.13 
                 0.14 
                 Yes 
                 Yes 
               
               
                 Q571S 
                 0.25 
                 0.09 
                 0.20 
                 0.09 
                 0.89 
                 0.23 
                 Yes 
                 Yes 
               
               
                 Q571T 
                 0.22 
                 0.13 
                 0.19 
                 0.13 
                 0.87 
                 0.41 
                 Yes 
                 Yes 
               
               
                 Q571R 
                 −0.03 
                 0.04 
                 −0.43 
                 0.05 
                 0.19 
                 0.10 
                 Yes 
                 No 
               
               
                 Q571C 
                 −0.60 
                 0.16 
                 0.23 
                 0.12 
                 −0.33 
                 0.24 
                 Yes 
                 No 
               
               
                 Q571E 
                 −0.22 
                 0.05 
                 −0.40 
                 0.06 
                 −0.17 
                 0.05 
                 No 
                 No 
               
               
                 Q571G 
                 0.00 
                 0.06 
                 −0.25 
                 0.06 
                 −0.41 
                 0.18 
                 No 
                 No 
               
               
                 Q571H 
                 −0.23 
                 0.11 
                 −0.65 
                 0.12 
                 0.06 
                 0.24 
                 Yes 
                 No 
               
               
                 Q571L 
                 −0.41 
                 0.07 
                 −0.45 
                 0.07 
                 −0.66 
                 0.11 
                 No 
                 No 
               
               
                 Q571K 
                 −0.47 
                 0.16 
                 −0.33 
                 0.15 
                 0.08 
                 0.31 
                 Yes 
                 No 
               
               
                 Q571* 
                 −0.59 
                 0.11 
                 −0.27 
                 0.10 
                 −0.67 
                 0.17 
                 No 
                 No 
               
               
                 Q571W 
                 −0.09 
                 0.08 
                 −0.80 
                 0.09 
                 −0.51 
                 0.24 
                 No 
                 No 
               
               
                 Q571V 
                 −0.36 
                 0.11 
                 −0.20 
                 0.10 
                 −0.44 
                 0.32 
                 No 
                 No 
               
               
                 K572E 
                 0.11 
                 0.04 
                 0.25 
                 0.04 
                 0.42 
                 0.08 
                 Yes 
                 Yes 
               
               
                 K572A 
                 −0.24 
                 0.04 
                 0.33 
                 0.04 
                 −0.11 
                 0.11 
                 Yes 
                 No 
               
               
                 K572R 
                 −0.08 
                 0.03 
                 −0.05 
                 0.03 
                 0.03 
                 0.03 
                 Yes 
                 No 
               
               
                 K572N 
                 −0.17 
                 0.07 
                 0.17 
                 0.06 
                 0.02 
                 0.11 
                 Yes 
                 No 
               
               
                 K572D 
                 −0.09 
                 0.09 
                 0.03 
                 0.08 
                 0.45 
                 0.19 
                 Yes 
                 No 
               
               
                 K572C 
                 0.23 
                 0.07 
                 −0.87 
                 0.09 
                 −0.19 
                 0.25 
                 Yes 
                 No 
               
               
                 K572Q 
                 −0.21 
                 0.06 
                 0.11 
                 0.06 
                 0.37 
                 0.16 
                 Yes 
                 No 
               
               
                 K572G 
                 −0.17 
                 0.03 
                 −0.08 
                 0.03 
                 0.42 
                 0.03 
                 Yes 
                 No 
               
               
                 K572H 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.11 
                 0.33 
                 Yes 
                 No 
               
               
                 K572L 
                 −0.11 
                 0.05 
                 0.16 
                 0.05 
                 −0.32 
                 0.15 
                 Yes 
                 No 
               
               
                 K572M 
                 −0.71 
                 0.08 
                 0.02 
                 0.06 
                 0.21 
                 0.06 
                 Yes 
                 No 
               
               
                 K572P 
                 0.09 
                 0.06 
                 0.91 
                 0.06 
                 −0.88 
                 0.23 
                 Yes 
                 No 
               
               
                 K572S 
                 0.30 
                 0.05 
                 0.01 
                 0.05 
                 −0.29 
                 0.15 
                 Yes 
                 No 
               
               
                 K572* 
                 −1.34 
                 0.08 
                 −0.86 
                 0.07 
                 −0.86 
                 0.08 
                 No 
                 No 
               
               
                 K572T 
                 −0.04 
                 0.04 
                 −0.09 
                 0.04 
                 −0.24 
                 0.07 
                 No 
                 No 
               
               
                 K572W 
                 −0.46 
                 0.05 
                 −0.47 
                 0.05 
                 −0.68 
                 0.14 
                 No 
                 No 
               
               
                 K572Y 
                 −1.04 
                 0.16 
                 −1.01 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K572V 
                 −0.08 
                 0.04 
                 −0.31 
                 0.04 
                 −0.71 
                 0.04 
                 No 
                 No 
               
               
                 G573A 
                 0.04 
                 0.04 
                 −0.11 
                 0.04 
                 −0.99 
                 0.09 
                 Yes 
                 No 
               
               
                 G573R 
                 −0.04 
                 0.03 
                 −0.31 
                 0.04 
                 −0.66 
                 0.08 
                 No 
                 No 
               
               
                 G573N 
                 0.45 
                 0.12 
                 −0.94 
                 0.17 
                 −0.29 
                 0.41 
                 Yes 
                 No 
               
               
                 G573D 
                 −0.05 
                 0.06 
                 −0.41 
                 0.07 
                 −0.95 
                 0.13 
                 No 
                 No 
               
               
                 G573C 
                 −0.22 
                 0.06 
                 −0.35 
                 0.06 
                 −0.42 
                 0.11 
                 No 
                 No 
               
               
                 G573Q 
                 0.40 
                 0.07 
                 −0.29 
                 0.08 
                 −0.43 
                 0.26 
                 Yes 
                 No 
               
               
                 G573E 
                 −0.09 
                 0.05 
                 0.36 
                 0.05 
                 −0.50 
                 0.08 
                 Yes 
                 No 
               
               
                 G573H 
                 −0.77 
                 0.12 
                 0.37 
                 0.09 
                 −0.51 
                 0.30 
                 Yes 
                 No 
               
               
                 G573L 
                 −0.04 
                 0.05 
                 0.07 
                 0.05 
                 −0.43 
                 0.05 
                 Yes 
                 No 
               
               
                 G573K 
                 −1.43 
                 0.13 
                 −0.29 
                 0.09 
                 −0.32 
                 0.25 
                 No 
                 No 
               
               
                 G573M 
                 −0.32 
                 0.10 
                 −0.32 
                 0.09 
                 −0.28 
                 0.26 
                 No 
                 No 
               
               
                 G573F 
                 −0.45 
                 0.14 
                 −0.19 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G573P 
                 0.16 
                 0.06 
                 −0.38 
                 0.06 
                 −0.10 
                 0.21 
                 Yes 
                 No 
               
               
                 G573S 
                 0.11 
                 0.04 
                 −0.42 
                 0.05 
                 −0.55 
                 0.10 
                 Yes 
                 No 
               
               
                 G573* 
                 −1.18 
                 0.12 
                 −1.27 
                 0.12 
                 −0.75 
                 0.28 
                 No 
                 No 
               
               
                 G573T 
                 0.02 
                 0.08 
                 −0.53 
                 0.09 
                 −0.62 
                 0.08 
                 Yes 
                 No 
               
               
                 G573W 
                 −0.08 
                 0.05 
                 −0.60 
                 0.05 
                 −0.67 
                 0.09 
                 No 
                 No 
               
               
                 G573Y 
                 0.13 
                 0.11 
                 −0.81 
                 0.14 
                 −0.48 
                 0.30 
                 Yes 
                 No 
               
               
                 G573V 
                 −0.06 
                 0.04 
                 −0.40 
                 0.04 
                 −0.71 
                 0.06 
                 No 
                 No 
               
               
                 R574A 
                 −0.83 
                 0.07 
                 −0.54 
                 0.06 
                 −0.64 
                 0.10 
                 No 
                 No 
               
               
                 R574N 
                 −0.85 
                 0.17 
                 −0.69 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R574D 
                 −0.32 
                 0.10 
                 −1.05 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R574C 
                 0.58 
                 0.07 
                 0.15 
                 0.07 
                 −1.16 
                 0.22 
                 Yes 
                 No 
               
               
                 R574Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.08 
                 0.26 
                 Yes 
                 No 
               
               
                 R574E 
                 −0.53 
                 0.08 
                 −0.38 
                 0.07 
                 −1.34 
                 0.15 
                 No 
                 No 
               
               
                 R574G 
                 −0.21 
                 0.03 
                 −0.27 
                 0.03 
                 −0.60 
                 0.07 
                 No 
                 No 
               
               
                 R574I 
                 −0.50 
                 0.11 
                 −0.47 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R574L 
                 −0.36 
                 0.07 
                 −0.25 
                 0.07 
                 −0.78 
                 0.18 
                 No 
                 No 
               
               
                 R574K 
                 −0.33 
                 0.08 
                 0.42 
                 0.06 
                 −0.33 
                 0.17 
                 Yes 
                 No 
               
               
                 R574M 
                 0.51 
                 0.07 
                 −0.36 
                 0.08 
                 −0.64 
                 0.07 
                 Yes 
                 No 
               
               
                 R574F 
                 0.06 
                 0.12 
                 −0.99 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R574P 
                 −0.38 
                 0.13 
                 0.11 
                 0.11 
                 −0.72 
                 0.23 
                 Yes 
                 No 
               
               
                 R574S 
                 0.12 
                 0.04 
                 0.02 
                 0.04 
                 −1.04 
                 0.03 
                 Yes 
                 No 
               
               
                 R574* 
                 −0.34 
                 0.07 
                 −0.51 
                 0.07 
                 −0.84 
                 0.09 
                 No 
                 No 
               
               
                 R574T 
                 −0.65 
                 0.09 
                 0.35 
                 0.07 
                 −0.83 
                 0.16 
                 Yes 
                 No 
               
               
                 R574W 
                 −0.10 
                 0.05 
                 −0.10 
                 0.05 
                 −0.73 
                 0.06 
                 No 
                 No 
               
               
                 R574Y 
                 −0.25 
                 0.12 
                 0.13 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R574V 
                 0.59 
                 0.05 
                 −0.27 
                 0.05 
                 −1.08 
                 0.14 
                 Yes 
                 No 
               
               
                 Y575G 
                 0.53 
                 0.04 
                 0.21 
                 0.04 
                 0.32 
                 0.07 
                 Yes 
                 Yes 
               
               
                 Y575M 
                 0.89 
                 0.11 
                 0.27 
                 0.12 
                 0.31 
                 0.41 
                 Yes 
                 Yes 
               
               
                 Y575A 
                 0.55 
                 0.05 
                 0.01 
                 0.06 
                 −0.07 
                 0.18 
                 Yes 
                 No 
               
               
                 Y575R 
                 0.15 
                 0.05 
                 −0.04 
                 0.06 
                 −0.56 
                 0.10 
                 Yes 
                 No 
               
               
                 Y575N 
                 −0.07 
                 0.10 
                 0.34 
                 0.09 
                 −0.21 
                 0.10 
                 Yes 
                 No 
               
               
                 Y575D 
                 −0.07 
                 0.09 
                 0.15 
                 0.09 
                 −0.45 
                 0.25 
                 Yes 
                 No 
               
               
                 Y575C 
                 0.20 
                 0.06 
                 0.17 
                 0.06 
                 −0.26 
                 0.09 
                 Yes 
                 No 
               
               
                 Y575Q 
                 −0.22 
                 0.13 
                 −0.32 
                 0.13 
                 −0.16 
                 0.30 
                 No 
                 No 
               
               
                 Y575E 
                 0.03 
                 0.08 
                 −0.32 
                 0.09 
                 −0.41 
                 0.35 
                 Yes 
                 No 
               
               
                 Y575H 
                 −0.24 
                 0.08 
                 −0.29 
                 0.08 
                 0.23 
                 0.13 
                 Yes 
                 No 
               
               
                 Y575I 
                 0.04 
                 0.14 
                 −0.37 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y575L 
                 −0.05 
                 0.07 
                 −0.43 
                 0.08 
                 −0.22 
                 0.23 
                 No 
                 No 
               
               
                 Y575K 
                 0.95 
                 0.11 
                 0.22 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y575F 
                 0.14 
                 0.08 
                 −0.45 
                 0.09 
                 −0.16 
                 0.12 
                 Yes 
                 No 
               
               
                 Y575P 
                 −0.06 
                 0.09 
                 −0.22 
                 0.09 
                 −0.14 
                 0.31 
                 No 
                 No 
               
               
                 Y575S 
                 0.02 
                 0.06 
                 0.01 
                 0.06 
                 −0.07 
                 0.09 
                 Yes 
                 No 
               
               
                 Y575* 
                 −0.20 
                 0.07 
                 −0.46 
                 0.08 
                 −0.51 
                 0.12 
                 No 
                 No 
               
               
                 Y575T 
                 −0.55 
                 0.10 
                 −0.40 
                 0.09 
                 −0.14 
                 0.30 
                 No 
                 No 
               
               
                 Y575W 
                 −0.44 
                 0.09 
                 0.31 
                 0.07 
                 −0.36 
                 0.16 
                 Yes 
                 No 
               
               
                 Y575V 
                 −0.10 
                 0.07 
                 −0.35 
                 0.07 
                 −0.29 
                 0.24 
                 No 
                 No 
               
               
                 K576C 
                 0.27 
                 0.07 
                 0.25 
                 0.07 
                 0.10 
                 0.26 
                 Yes 
                 Yes 
               
               
                 K576A 
                 −0.05 
                 0.05 
                 0.16 
                 0.05 
                 0.27 
                 0.06 
                 Yes 
                 No 
               
               
                 K576R 
                 −0.31 
                 0.03 
                 −0.11 
                 0.03 
                 0.05 
                 0.07 
                 Yes 
                 No 
               
               
                 K576N 
                 −0.28 
                 0.08 
                 −0.47 
                 0.08 
                 −0.11 
                 0.15 
                 No 
                 No 
               
               
                 K576D 
                 −0.01 
                 0.08 
                 −0.22 
                 0.09 
                 −1.04 
                 0.26 
                 No 
                 No 
               
               
                 K576Q 
                 −0.06 
                 0.06 
                 0.02 
                 0.05 
                 0.57 
                 0.08 
                 Yes 
                 No 
               
               
                 K576E 
                 −0.63 
                 0.05 
                 −0.38 
                 0.05 
                 −0.27 
                 0.09 
                 No 
                 No 
               
               
                 K576G 
                 −0.03 
                 0.03 
                 −0.13 
                 0.03 
                 0.28 
                 0.04 
                 Yes 
                 No 
               
               
                 K576H 
                 −0.26 
                 0.14 
                 −0.46 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K576I 
                 0.10 
                 0.11 
                 −0.10 
                 0.12 
                 0.37 
                 0.16 
                 Yes 
                 No 
               
               
                 K576L 
                 −0.04 
                 0.05 
                 0.01 
                 0.04 
                 0.24 
                 0.05 
                 Yes 
                 No 
               
               
                 K576M 
                 0.21 
                 0.05 
                 −0.14 
                 0.06 
                 0.07 
                 0.09 
                 Yes 
                 No 
               
               
                 K576F 
                 −0.41 
                 0.13 
                 −1.12 
                 0.15 
                 0.20 
                 0.34 
                 Yes 
                 No 
               
               
                 K576P 
                 −0.07 
                 0.09 
                 −1.70 
                 0.14 
                 −0.15 
                 0.17 
                 No 
                 No 
               
               
                 K576S 
                 −0.20 
                 0.05 
                 −0.43 
                 0.06 
                 0.64 
                 0.15 
                 Yes 
                 No 
               
               
                 K576* 
                 −1.75 
                 0.10 
                 −1.41 
                 0.08 
                 −0.09 
                 0.15 
                 No 
                 No 
               
               
                 K576T 
                 −0.05 
                 0.06 
                 0.30 
                 0.05 
                 0.20 
                 0.08 
                 Yes 
                 No 
               
               
                 K576W 
                 −0.33 
                 0.05 
                 −0.65 
                 0.05 
                 −0.56 
                 0.13 
                 No 
                 No 
               
               
                 K576Y 
                 −1.23 
                 0.16 
                 −0.48 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K576V 
                 −0.36 
                 0.04 
                 −0.69 
                 0.05 
                 0.38 
                 0.07 
                 Yes 
                 No 
               
               
                 A577R 
                 −0.12 
                 0.03 
                 −0.60 
                 0.04 
                 0.88 
                 0.06 
                 Yes 
                 No 
               
               
                 A577N 
                 0.11 
                 0.09 
                 −0.85 
                 0.11 
                 0.34 
                 0.13 
                 Yes 
                 No 
               
               
                 A577D 
                 −0.06 
                 0.05 
                 −0.11 
                 0.05 
                 −0.37 
                 0.13 
                 No 
                 No 
               
               
                 A577C 
                 −0.24 
                 0.06 
                 −0.02 
                 0.06 
                 −0.39 
                 0.20 
                 No 
                 No 
               
               
                 A577Q 
                 −0.37 
                 0.07 
                 0.63 
                 0.06 
                 0.10 
                 0.23 
                 Yes 
                 No 
               
               
                 A577E 
                 −0.66 
                 0.05 
                 −2.12 
                 0.09 
                 −0.27 
                 0.14 
                 No 
                 No 
               
               
                 A577G 
                 0.22 
                 0.02 
                 −0.05 
                 0.03 
                 0.49 
                 0.05 
                 Yes 
                 No 
               
               
                 A577H 
                 0.02 
                 0.08 
                 −0.59 
                 0.10 
                 0.25 
                 0.22 
                 Yes 
                 No 
               
               
                 A577I 
                 −0.94 
                 0.12 
                 −0.35 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A577L 
                 −0.90 
                 0.06 
                 −0.37 
                 0.05 
                 −0.15 
                 0.06 
                 No 
                 No 
               
               
                 A577K 
                 −0.40 
                 0.08 
                 −0.80 
                 0.09 
                 1.09 
                 0.07 
                 Yes 
                 No 
               
               
                 A577M 
                 −0.40 
                 0.08 
                 −0.20 
                 0.07 
                 −0.28 
                 0.20 
                 No 
                 No 
               
               
                 A577F 
                 −0.79 
                 0.11 
                 −0.99 
                 0.12 
                 −0.78 
                 0.19 
                 No 
                 No 
               
               
                 A577P 
                 −0.25 
                 0.06 
                 −0.11 
                 0.05 
                 −0.29 
                 0.11 
                 No 
                 No 
               
               
                 A577S 
                 −0.31 
                 0.04 
                 −0.26 
                 0.04 
                 0.08 
                 0.10 
                 Yes 
                 No 
               
               
                 A577* 
                 −1.65 
                 0.11 
                 −1.75 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A577T 
                 −0.09 
                 0.05 
                 −0.38 
                 0.05 
                 −0.02 
                 0.08 
                 No 
                 No 
               
               
                 A577W 
                 −0.63 
                 0.05 
                 −0.66 
                 0.05 
                 −0.66 
                 0.08 
                 No 
                 No 
               
               
                 A577Y 
                 −0.22 
                 0.09 
                 −0.20 
                 0.09 
                 0.05 
                 0.32 
                 Yes 
                 No 
               
               
                 A577V 
                 −0.06 
                 0.03 
                 −0.28 
                 0.04 
                 −0.42 
                 0.09 
                 No 
                 No 
               
               
                 L578A 
                 −0.22 
                 0.03 
                 −0.43 
                 0.03 
                 −0.20 
                 0.07 
                 No 
                 No 
               
               
                 L578R 
                 −0.11 
                 0.02 
                 −0.49 
                 0.02 
                 0.04 
                 0.03 
                 Yes 
                 No 
               
               
                 L578N 
                 −0.35 
                 0.11 
                 −0.09 
                 0.10 
                 −0.47 
                 0.23 
                 No 
                 No 
               
               
                 L578D 
                 −0.09 
                 0.06 
                 −0.41 
                 0.06 
                 −0.92 
                 0.07 
                 No 
                 No 
               
               
                 L578C 
                 0.05 
                 0.04 
                 −0.34 
                 0.05 
                 −0.03 
                 0.10 
                 Yes 
                 No 
               
               
                 L578Q 
                 0.11 
                 0.04 
                 −0.12 
                 0.05 
                 0.00 
                 0.10 
                 Yes 
                 No 
               
               
                 L578E 
                 −0.33 
                 0.04 
                 −0.53 
                 0.04 
                 −0.77 
                 0.12 
                 No 
                 No 
               
               
                 L578G 
                 −0.26 
                 0.02 
                 −0.45 
                 0.02 
                 −0.29 
                 0.02 
                 No 
                 No 
               
               
                 L578H 
                 −0.27 
                 0.07 
                 0.10 
                 0.06 
                 0.03 
                 0.14 
                 Yes 
                 No 
               
               
                 L578I 
                 −0.28 
                 0.09 
                 0.32 
                 0.08 
                 0.22 
                 0.23 
                 Yes 
                 No 
               
               
                 L578K 
                 −0.62 
                 0.07 
                 −1.21 
                 0.09 
                 0.50 
                 0.20 
                 Yes 
                 No 
               
               
                 L578M 
                 −0.12 
                 0.03 
                 −0.21 
                 0.03 
                 −0.03 
                 0.05 
                 No 
                 No 
               
               
                 L578F 
                 0.36 
                 0.06 
                 0.21 
                 0.06 
                 −0.12 
                 0.14 
                 Yes 
                 No 
               
               
                 L578P 
                 −0.62 
                 0.05 
                 0.03 
                 0.04 
                 −0.31 
                 0.06 
                 Yes 
                 No 
               
               
                 L578S 
                 −0.37 
                 0.04 
                 −0.33 
                 0.04 
                 −0.08 
                 0.09 
                 No 
                 No 
               
               
                 L578* 
                 −1.90 
                 0.09 
                 −1.28 
                 0.07 
                 −1.24 
                 0.09 
                 No 
                 No 
               
               
                 L578T 
                 −0.29 
                 0.06 
                 −0.06 
                 0.05 
                 0.26 
                 0.06 
                 Yes 
                 No 
               
               
                 L578W 
                 −0.37 
                 0.03 
                 −0.41 
                 0.03 
                 −0.08 
                 0.04 
                 No 
                 No 
               
               
                 L578Y 
                 0.36 
                 0.07 
                 −0.21 
                 0.07 
                 −0.24 
                 0.07 
                 Yes 
                 No 
               
               
                 L578V 
                 −0.19 
                 0.03 
                 −0.28 
                 0.03 
                 0.01 
                 0.04 
                 Yes 
                 No 
               
               
                 S579T 
                 0.17 
                 0.04 
                 0.33 
                 0.04 
                 0.01 
                 0.06 
                 Yes 
                 Yes 
               
               
                 S579V 
                 0.04 
                 0.03 
                 0.02 
                 0.03 
                 0.05 
                 0.07 
                 Yes 
                 Yes 
               
               
                 S579A 
                 −0.06 
                 0.03 
                 0.06 
                 0.02 
                 0.08 
                 0.03 
                 Yes 
                 No 
               
               
                 S579R 
                 0.04 
                 0.03 
                 −0.11 
                 0.03 
                 −0.15 
                 0.05 
                 Yes 
                 No 
               
               
                 S579N 
                 −0.19 
                 0.07 
                 −0.45 
                 0.08 
                 −0.39 
                 0.23 
                 No 
                 No 
               
               
                 S579D 
                 −0.39 
                 0.06 
                 −0.43 
                 0.06 
                 0.03 
                 0.06 
                 Yes 
                 No 
               
               
                 S579C 
                 0.02 
                 0.03 
                 0.07 
                 0.03 
                 −0.02 
                 0.05 
                 Yes 
                 No 
               
               
                 S579Q 
                 −0.19 
                 0.07 
                 −0.66 
                 0.08 
                 0.30 
                 0.20 
                 Yes 
                 No 
               
               
                 S579E 
                 −0.10 
                 0.04 
                 −0.54 
                 0.05 
                 −0.15 
                 0.05 
                 No 
                 No 
               
               
                 S579G 
                 −0.25 
                 0.03 
                 −0.12 
                 0.02 
                 0.11 
                 0.05 
                 Yes 
                 No 
               
               
                 S579H 
                 0.09 
                 0.08 
                 −0.15 
                 0.08 
                 −0.18 
                 0.12 
                 Yes 
                 No 
               
               
                 S579I 
                 −0.05 
                 0.06 
                 0.25 
                 0.06 
                 0.04 
                 0.15 
                 Yes 
                 No 
               
               
                 S579L 
                 −0.65 
                 0.04 
                 −0.32 
                 0.04 
                 0.11 
                 0.05 
                 Yes 
                 No 
               
               
                 S579K 
                 −0.15 
                 0.06 
                 −0.55 
                 0.07 
                 0.13 
                 0.22 
                 Yes 
                 No 
               
               
                 S579M 
                 −0.18 
                 0.06 
                 0.05 
                 0.05 
                 0.28 
                 0.19 
                 Yes 
                 No 
               
               
                 S579F 
                 0.27 
                 0.04 
                 0.16 
                 0.04 
                 −0.08 
                 0.07 
                 Yes 
                 No 
               
               
                 S579P 
                 −0.19 
                 0.05 
                 −0.75 
                 0.05 
                 −0.05 
                 0.10 
                 No 
                 No 
               
               
                 S579* 
                 −1.34 
                 0.08 
                 −1.06 
                 0.07 
                 −1.30 
                 0.11 
                 No 
                 No 
               
               
                 S579W 
                 −0.09 
                 0.04 
                 −0.35 
                 0.04 
                 −0.37 
                 0.06 
                 No 
                 No 
               
               
                 S579Y 
                 −0.06 
                 0.05 
                 −0.21 
                 0.05 
                 −0.36 
                 0.04 
                 No 
                 No 
               
               
                 F580A 
                 −0.80 
                 0.08 
                 −0.25 
                 0.07 
                 −1.44 
                 0.19 
                 No 
                 No 
               
               
                 F580R 
                 −1.58 
                 0.09 
                 −1.48 
                 0.08 
                 −1.26 
                 0.19 
                 No 
                 No 
               
               
                 F580C 
                 −0.22 
                 0.09 
                 −0.47 
                 0.10 
                 −0.11 
                 0.18 
                 No 
                 No 
               
               
                 F580E 
                 −0.96 
                 0.12 
                 −0.21 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F580G 
                 −0.91 
                 0.05 
                 −1.05 
                 0.05 
                 −1.21 
                 0.04 
                 No 
                 No 
               
               
                 F580I 
                 −0.14 
                 0.09 
                 −0.06 
                 0.09 
                 −0.17 
                 0.28 
                 No 
                 No 
               
               
                 F580L 
                 −0.11 
                 0.05 
                 −0.28 
                 0.05 
                 0.01 
                 0.09 
                 Yes 
                 No 
               
               
                 F580M 
                 0.31 
                 0.12 
                 −0.37 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F580P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.75 
                 0.28 
                 Yes 
                 No 
               
               
                 F580S 
                 −0.22 
                 0.07 
                 −0.70 
                 0.07 
                 −0.67 
                 0.10 
                 No 
                 No 
               
               
                 F580W 
                 −1.14 
                 0.10 
                 0.30 
                 0.07 
                 0.67 
                 0.24 
                 Yes 
                 No 
               
               
                 F580Y 
                 0.39 
                 0.11 
                 −0.45 
                 0.14 
                 −0.09 
                 0.23 
                 Yes 
                 No 
               
               
                 F580V 
                 0.18 
                 0.06 
                 −0.33 
                 0.06 
                 −0.52 
                 0.13 
                 Yes 
                 No 
               
               
                 E581A 
                 −0.08 
                 0.03 
                 0.16 
                 0.03 
                 −0.13 
                 0.06 
                 Yes 
                 No 
               
               
                 E581R 
                 −0.31 
                 0.03 
                 −0.14 
                 0.03 
                 −0.36 
                 0.04 
                 No 
                 No 
               
               
                 E581N 
                 −0.14 
                 0.15 
                 0.56 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E581D 
                 0.04 
                 0.06 
                 0.25 
                 0.06 
                 −0.21 
                 0.09 
                 Yes 
                 No 
               
               
                 E581C 
                 0.12 
                 0.07 
                 0.54 
                 0.06 
                 −0.12 
                 0.15 
                 Yes 
                 No 
               
               
                 E581Q 
                 0.01 
                 0.04 
                 0.09 
                 0.04 
                 −0.12 
                 0.06 
                 Yes 
                 No 
               
               
                 E581G 
                 −0.15 
                 0.02 
                 −0.05 
                 0.02 
                 −0.03 
                 0.03 
                 No 
                 No 
               
               
                 E581H 
                 −0.31 
                 0.12 
                 1.00 
                 0.10 
                 −0.67 
                 0.35 
                 Yes 
                 No 
               
               
                 E581I 
                 −0.12 
                 0.14 
                 0.03 
                 0.13 
                 0.40 
                 0.44 
                 Yes 
                 No 
               
               
                 E581L 
                 0.09 
                 0.04 
                 −0.12 
                 0.04 
                 0.29 
                 0.12 
                 Yes 
                 No 
               
               
                 E581K 
                 −0.10 
                 0.05 
                 −0.02 
                 0.05 
                 −0.33 
                 0.07 
                 No 
                 No 
               
               
                 E581M 
                 −0.05 
                 0.08 
                 −0.79 
                 0.09 
                 0.12 
                 0.13 
                 Yes 
                 No 
               
               
                 E581F 
                 −0.32 
                 0.11 
                 −0.09 
                 0.10 
                 −0.40 
                 0.30 
                 No 
                 No 
               
               
                 E581P 
                 −0.49 
                 0.07 
                 −0.09 
                 0.06 
                 −0.25 
                 0.13 
                 No 
                 No 
               
               
                 E581S 
                 0.00 
                 0.05 
                 −1.01 
                 0.06 
                 −0.11 
                 0.06 
                 Yes 
                 No 
               
               
                 E581* 
                 −1.00 
                 0.07 
                 −0.93 
                 0.07 
                 −0.92 
                 0.13 
                 No 
                 No 
               
               
                 E581T 
                 −0.23 
                 0.07 
                 −0.29 
                 0.07 
                 0.06 
                 0.09 
                 Yes 
                 No 
               
               
                 E581W 
                 0.25 
                 0.04 
                 −0.31 
                 0.04 
                 0.04 
                 0.05 
                 Yes 
                 No 
               
               
                 E581Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.25 
                 0.28 
                 Yes 
                 No 
               
               
                 E581V 
                 −0.18 
                 0.04 
                 0.31 
                 0.03 
                 0.26 
                 0.10 
                 Yes 
                 No 
               
               
                 P582A 
                 −0.46 
                 0.07 
                 −0.64 
                 0.07 
                 −0.60 
                 0.13 
                 No 
                 No 
               
               
                 P582R 
                 0.24 
                 0.05 
                 −0.24 
                 0.06 
                 −0.48 
                 0.17 
                 Yes 
                 No 
               
               
                 P582N 
                 −0.02 
                 0.05 
                 −0.24 
                 0.05 
                 −0.22 
                 0.11 
                 No 
                 No 
               
               
                 P582D 
                 −0.41 
                 0.18 
                 −0.64 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P582C 
                 0.14 
                 0.11 
                 −0.07 
                 0.12 
                 0.17 
                 0.64 
                 Yes 
                 No 
               
               
                 P582Q 
                 −0.74 
                 0.13 
                 −0.13 
                 0.11 
                 −0.07 
                 0.25 
                 No 
                 No 
               
               
                 P582G 
                 −0.10 
                 0.06 
                 −0.80 
                 0.07 
                 −0.50 
                 0.18 
                 No 
                 No 
               
               
                 P582H 
                 −0.03 
                 0.02 
                 −0.15 
                 0.02 
                 −0.12 
                 0.04 
                 No 
                 No 
               
               
                 P582L 
                 −0.14 
                 0.07 
                 −0.96 
                 0.08 
                 −0.26 
                 0.13 
                 No 
                 No 
               
               
                 P582K 
                 −0.33 
                 0.19 
                 0.97 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P582F 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.02 
                 0.55 
                 Yes 
                 No 
               
               
                 P582S 
                 0.19 
                 0.06 
                 0.48 
                 0.05 
                 −1.33 
                 0.16 
                 Yes 
                 No 
               
               
                 P582T 
                 −0.13 
                 0.03 
                 −0.19 
                 0.03 
                 −0.48 
                 0.06 
                 No 
                 No 
               
               
                 P582W 
                 −1.46 
                 0.15 
                 −0.73 
                 0.11 
                 −0.12 
                 0.35 
                 No 
                 No 
               
               
                 P582V 
                 −0.90 
                 0.10 
                 −0.27 
                 0.08 
                 −0.81 
                 0.09 
                 No 
                 No 
               
               
                 T583I 
                 0.04 
                 0.08 
                 0.11 
                 0.07 
                 0.07 
                 0.17 
                 Yes 
                 Yes 
               
               
                 T583A 
                 0.02 
                 0.04 
                 −0.22 
                 0.04 
                 −0.17 
                 0.08 
                 Yes 
                 No 
               
               
                 T583R 
                 0.12 
                 0.05 
                 −0.31 
                 0.05 
                 −0.04 
                 0.09 
                 Yes 
                 No 
               
               
                 T583N 
                 0.00 
                 0.06 
                 0.01 
                 0.06 
                 −0.20 
                 0.09 
                 Yes 
                 No 
               
               
                 T583D 
                 0.23 
                 0.12 
                 −0.96 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T583C 
                 0.67 
                 0.09 
                 −0.82 
                 0.12 
                 −0.67 
                 0.27 
                 Yes 
                 No 
               
               
                 T583Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.28 
                 0.36 
                 Yes 
                 No 
               
               
                 T583E 
                 −0.62 
                 0.10 
                 0.01 
                 0.09 
                 −0.72 
                 0.28 
                 Yes 
                 No 
               
               
                 T583G 
                 −0.17 
                 0.05 
                 −0.35 
                 0.05 
                 0.16 
                 0.06 
                 Yes 
                 No 
               
               
                 T583L 
                 −0.09 
                 0.06 
                 −0.72 
                 0.07 
                 −0.24 
                 0.22 
                 No 
                 No 
               
               
                 T583K 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.15 
                 0.44 
                 Yes 
                 No 
               
               
                 T583M 
                 −0.72 
                 0.13 
                 −0.89 
                 0.14 
                 −0.12 
                 0.32 
                 No 
                 No 
               
               
                 T583F 
                 −0.41 
                 0.13 
                 −0.83 
                 0.15 
                 −0.13 
                 0.36 
                 No 
                 No 
               
               
                 T583P 
                 −0.14 
                 0.08 
                 −0.64 
                 0.08 
                 −0.37 
                 0.14 
                 No 
                 No 
               
               
                 T583S 
                 0.18 
                 0.05 
                 0.11 
                 0.05 
                 −0.34 
                 0.07 
                 Yes 
                 No 
               
               
                 T583W 
                 −0.31 
                 0.07 
                 −0.54 
                 0.08 
                 −0.09 
                 0.08 
                 No 
                 No 
               
               
                 T583V 
                 0.01 
                 0.06 
                 −0.05 
                 0.06 
                 0.15 
                 0.22 
                 Yes 
                 No 
               
               
                 E584H 
                 0.09 
                 0.07 
                 0.22 
                 0.07 
                 0.17 
                 0.14 
                 Yes 
                 Yes 
               
               
                 E584V 
                 0.10 
                 0.03 
                 0.06 
                 0.03 
                 0.12 
                 0.04 
                 Yes 
                 Yes 
               
               
                 E584A 
                 −0.01 
                 0.03 
                 0.09 
                 0.03 
                 0.10 
                 0.06 
                 Yes 
                 No 
               
               
                 E584R 
                 −0.23 
                 0.03 
                 −0.12 
                 0.03 
                 −0.10 
                 0.05 
                 No 
                 No 
               
               
                 E584N 
                 −0.50 
                 0.09 
                 −0.38 
                 0.08 
                 −0.11 
                 0.20 
                 No 
                 No 
               
               
                 E584D 
                 0.46 
                 0.04 
                 0.51 
                 0.04 
                 −0.02 
                 0.08 
                 Yes 
                 No 
               
               
                 E584C 
                 −0.03 
                 0.05 
                 0.09 
                 0.05 
                 0.13 
                 0.07 
                 Yes 
                 No 
               
               
                 E584Q 
                 0.09 
                 0.07 
                 −0.88 
                 0.08 
                 −0.09 
                 0.10 
                 Yes 
                 No 
               
               
                 E584G 
                 −0.02 
                 0.02 
                 0.06 
                 0.02 
                 0.16 
                 0.04 
                 Yes 
                 No 
               
               
                 E584I 
                 0.32 
                 0.07 
                 −0.34 
                 0.08 
                 −0.03 
                 0.20 
                 Yes 
                 No 
               
               
                 E584L 
                 −0.27 
                 0.04 
                 0.00 
                 0.04 
                 −0.06 
                 0.10 
                 No 
                 No 
               
               
                 E584K 
                 −0.29 
                 0.06 
                 −0.78 
                 0.07 
                 0.39 
                 0.09 
                 Yes 
                 No 
               
               
                 E584M 
                 −0.17 
                 0.07 
                 −0.68 
                 0.08 
                 0.34 
                 0.13 
                 Yes 
                 No 
               
               
                 E584F 
                 −0.11 
                 0.08 
                 −0.41 
                 0.09 
                 0.27 
                 0.19 
                 Yes 
                 No 
               
               
                 E584P 
                 0.12 
                 0.05 
                 −0.13 
                 0.06 
                 −0.24 
                 0.17 
                 Yes 
                 No 
               
               
                 E584S 
                 −0.44 
                 0.04 
                 0.09 
                 0.04 
                 0.26 
                 0.09 
                 Yes 
                 No 
               
               
                 E584* 
                 −1.22 
                 0.09 
                 −1.26 
                 0.08 
                 −1.15 
                 0.13 
                 No 
                 No 
               
               
                 E584T 
                 −0.03 
                 0.05 
                 −0.03 
                 0.05 
                 0.17 
                 0.15 
                 Yes 
                 No 
               
               
                 E584W 
                 −0.73 
                 0.06 
                 −0.52 
                 0.05 
                 −0.32 
                 0.07 
                 No 
                 No 
               
               
                 E584Y 
                 −0.13 
                 0.07 
                 0.55 
                 0.06 
                 0.05 
                 0.25 
                 Yes 
                 No 
               
               
                 K585R 
                 0.07 
                 0.03 
                 0.32 
                 0.03 
                 0.06 
                 0.05 
                 Yes 
                 Yes 
               
               
                 K585F 
                 0.51 
                 0.09 
                 0.04 
                 0.09 
                 0.61 
                 0.36 
                 Yes 
                 Yes 
               
               
                 K585A 
                 0.21 
                 0.04 
                 −0.23 
                 0.05 
                 0.16 
                 0.13 
                 Yes 
                 No 
               
               
                 K585N 
                 −0.13 
                 0.09 
                 0.18 
                 0.08 
                 −0.67 
                 0.12 
                 Yes 
                 No 
               
               
                 K585D 
                 −0.05 
                 0.07 
                 −0.08 
                 0.07 
                 −0.05 
                 0.23 
                 No 
                 No 
               
               
                 K585C 
                 −0.25 
                 0.07 
                 −0.61 
                 0.08 
                 −0.11 
                 0.29 
                 No 
                 No 
               
               
                 K585Q 
                 0.07 
                 0.06 
                 0.41 
                 0.06 
                 −0.09 
                 0.08 
                 Yes 
                 No 
               
               
                 K585E 
                 −0.33 
                 0.05 
                 −0.44 
                 0.05 
                 0.10 
                 0.12 
                 Yes 
                 No 
               
               
                 K585G 
                 −0.18 
                 0.03 
                 −0.04 
                 0.03 
                 0.16 
                 0.04 
                 Yes 
                 No 
               
               
                 K585H 
                 0.12 
                 0.11 
                 −0.60 
                 0.13 
                 0.28 
                 0.14 
                 Yes 
                 No 
               
               
                 K585I 
                 −1.45 
                 0.14 
                 0.35 
                 0.08 
                 0.11 
                 0.25 
                 Yes 
                 No 
               
               
                 K585L 
                 −0.10 
                 0.04 
                 −0.06 
                 0.04 
                 0.27 
                 0.13 
                 Yes 
                 No 
               
               
                 K585M 
                 −0.25 
                 0.07 
                 −0.05 
                 0.06 
                 0.21 
                 0.17 
                 Yes 
                 No 
               
               
                 K585P 
                 0.20 
                 0.06 
                 −0.04 
                 0.07 
                 0.15 
                 0.21 
                 Yes 
                 No 
               
               
                 K585S 
                 −0.17 
                 0.05 
                 0.24 
                 0.04 
                 0.20 
                 0.11 
                 Yes 
                 No 
               
               
                 K585* 
                 −0.91 
                 0.07 
                 −0.60 
                 0.06 
                 −0.61 
                 0.11 
                 No 
                 No 
               
               
                 K585T 
                 0.08 
                 0.05 
                 −0.30 
                 0.05 
                 0.05 
                 0.07 
                 Yes 
                 No 
               
               
                 K585W 
                 −0.21 
                 0.05 
                 −0.15 
                 0.05 
                 0.18 
                 0.16 
                 Yes 
                 No 
               
               
                 K585Y 
                 0.18 
                 0.10 
                 −0.92 
                 0.13 
                 0.07 
                 0.40 
                 Yes 
                 No 
               
               
                 K585V 
                 −0.16 
                 0.04 
                 −0.68 
                 0.04 
                 0.37 
                 0.06 
                 Yes 
                 No 
               
               
                 T586A 
                 −0.30 
                 0.05 
                 −0.02 
                 0.04 
                 −0.01 
                 0.11 
                 No 
                 No 
               
               
                 T586R 
                 −0.56 
                 0.05 
                 −0.06 
                 0.04 
                 −0.20 
                 0.14 
                 No 
                 No 
               
               
                 T586N 
                 −0.07 
                 0.05 
                 0.15 
                 0.05 
                 −0.02 
                 0.07 
                 Yes 
                 No 
               
               
                 T586D 
                 −0.41 
                 0.12 
                 1.10 
                 0.09 
                 0.41 
                 0.30 
                 Yes 
                 No 
               
               
                 T586C 
                 −0.60 
                 0.11 
                 −0.45 
                 0.10 
                 0.10 
                 0.29 
                 Yes 
                 No 
               
               
                 T586Q 
                 −0.65 
                 0.14 
                 0.28 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T586E 
                 −0.29 
                 0.09 
                 0.04 
                 0.08 
                 0.16 
                 0.37 
                 Yes 
                 No 
               
               
                 T586G 
                 −0.21 
                 0.04 
                 0.22 
                 0.03 
                 −0.07 
                 0.09 
                 Yes 
                 No 
               
               
                 T586I 
                 −0.77 
                 0.11 
                 0.90 
                 0.07 
                 −0.48 
                 0.19 
                 Yes 
                 No 
               
               
                 T586L 
                 −0.06 
                 0.06 
                 −0.85 
                 0.07 
                 0.01 
                 0.18 
                 Yes 
                 No 
               
               
                 T586K 
                 −0.06 
                 0.12 
                 0.80 
                 0.10 
                 −0.12 
                 0.13 
                 Yes 
                 No 
               
               
                 T586M 
                 −0.62 
                 0.11 
                 −1.06 
                 0.13 
                 0.22 
                 0.34 
                 Yes 
                 No 
               
               
                 T586F 
                 0.21 
                 0.13 
                 −0.21 
                 0.14 
                 0.02 
                 0.54 
                 Yes 
                 No 
               
               
                 T586P 
                 0.38 
                 0.06 
                 −0.09 
                 0.06 
                 0.22 
                 0.12 
                 Yes 
                 No 
               
               
                 T586S 
                 −0.22 
                 0.05 
                 −0.08 
                 0.05 
                 0.01 
                 0.08 
                 Yes 
                 No 
               
               
                 T586W 
                 −0.48 
                 0.07 
                 −0.61 
                 0.07 
                 −0.29 
                 0.24 
                 No 
                 No 
               
               
                 T586Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.24 
                 0.26 
                 Yes 
                 No 
               
               
                 T586V 
                 −0.97 
                 0.07 
                 −0.13 
                 0.05 
                 0.13 
                 0.17 
                 Yes 
                 No 
               
               
                 S587A 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.45 
                 0.32 
                 Yes 
                 No 
               
               
                 S587R 
                 0.15 
                 0.08 
                 −0.61 
                 0.09 
                 −0.34 
                 0.15 
                 Yes 
                 No 
               
               
                 S587N 
                 −0.30 
                 0.13 
                 −0.31 
                 0.13 
                 −0.26 
                 0.18 
                 No 
                 No 
               
               
                 S587C 
                 0.01 
                 0.15 
                 0.00 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S587E 
                 0.33 
                 0.16 
                 −0.40 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S587G 
                 −0.32 
                 0.06 
                 −0.81 
                 0.07 
                 −0.21 
                 0.06 
                 No 
                 No 
               
               
                 S587L 
                 0.21 
                 0.14 
                 0.27 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S587T 
                 0.80 
                 0.11 
                 −0.41 
                 0.14 
                 −0.13 
                 0.23 
                 Yes 
                 No 
               
               
                 S587V 
                 0.20 
                 0.11 
                 −0.25 
                 0.12 
                 −0.04 
                 0.12 
                 Yes 
                 No 
               
               
                 E588A 
                 −0.01 
                 0.05 
                 0.25 
                 0.05 
                 0.17 
                 0.10 
                 Yes 
                 No 
               
               
                 E588R 
                 −0.39 
                 0.05 
                 −0.61 
                 0.05 
                 −0.31 
                 0.07 
                 No 
                 No 
               
               
                 E588D 
                 0.00 
                 0.08 
                 −0.12 
                 0.08 
                 −0.55 
                 0.13 
                 Yes 
                 No 
               
               
                 E588C 
                 −0.64 
                 0.11 
                 −0.35 
                 0.10 
                 0.00 
                 0.10 
                 No 
                 No 
               
               
                 E588Q 
                 0.11 
                 0.09 
                 −0.25 
                 0.09 
                 −0.08 
                 0.13 
                 Yes 
                 No 
               
               
                 E588G 
                 −0.16 
                 0.04 
                 −0.19 
                 0.04 
                 −0.34 
                 0.04 
                 No 
                 No 
               
               
                 E588H 
                 −0.35 
                 0.17 
                 −0.26 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E588L 
                 −0.31 
                 0.07 
                 −0.29 
                 0.07 
                 0.41 
                 0.12 
                 Yes 
                 No 
               
               
                 E588K 
                 0.18 
                 0.07 
                 0.13 
                 0.07 
                 −0.25 
                 0.15 
                 Yes 
                 No 
               
               
                 E588M 
                 −0.50 
                 0.12 
                 −0.10 
                 0.11 
                 0.54 
                 0.12 
                 Yes 
                 No 
               
               
                 E588F 
                 −0.23 
                 0.15 
                 0.13 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E588P 
                 −0.04 
                 0.10 
                 0.06 
                 0.09 
                 0.52 
                 0.19 
                 Yes 
                 No 
               
               
                 E588S 
                 −0.03 
                 0.07 
                 −0.34 
                 0.08 
                 −0.47 
                 0.08 
                 No 
                 No 
               
               
                 E588* 
                 −1.05 
                 0.11 
                 −1.06 
                 0.11 
                 −1.02 
                 0.15 
                 No 
                 No 
               
               
                 E588T 
                 0.32 
                 0.09 
                 −1.53 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E588W 
                 −0.02 
                 0.07 
                 0.03 
                 0.07 
                 −0.01 
                 0.19 
                 Yes 
                 No 
               
               
                 E588Y 
                 −0.11 
                 0.17 
                 0.93 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E588V 
                 −0.70 
                 0.06 
                 −0.19 
                 0.05 
                 0.07 
                 0.08 
                 Yes 
                 No 
               
               
                 G589A 
                 −0.44 
                 0.05 
                 −0.09 
                 0.04 
                 −0.52 
                 0.14 
                 No 
                 No 
               
               
                 G589R 
                 −0.21 
                 0.04 
                 −0.73 
                 0.04 
                 −0.69 
                 0.07 
                 No 
                 No 
               
               
                 G589D 
                 −0.29 
                 0.08 
                 −0.88 
                 0.10 
                 −0.70 
                 0.17 
                 No 
                 No 
               
               
                 G589C 
                 −0.14 
                 0.04 
                 −0.12 
                 0.04 
                 −0.59 
                 0.07 
                 No 
                 No 
               
               
                 G589Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.13 
                 0.27 
                 Yes 
                 No 
               
               
                 G589E 
                 −0.39 
                 0.06 
                 −1.47 
                 0.08 
                 −0.59 
                 0.24 
                 No 
                 No 
               
               
                 G589L 
                 0.07 
                 0.06 
                 −1.02 
                 0.08 
                 −1.07 
                 0.20 
                 Yes 
                 No 
               
               
                 G589M 
                 −0.45 
                 0.12 
                 −1.01 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G589P 
                 −0.34 
                 0.08 
                 −2.17 
                 0.15 
                 −1.08 
                 0.12 
                 No 
                 No 
               
               
                 G589S 
                 −0.13 
                 0.04 
                 −0.30 
                 0.04 
                 −0.54 
                 0.10 
                 No 
                 No 
               
               
                 G589T 
                 −0.52 
                 0.11 
                 −0.51 
                 0.10 
                 −1.12 
                 0.28 
                 No 
                 No 
               
               
                 G589W 
                 −0.62 
                 0.06 
                 −0.77 
                 0.07 
                 −0.26 
                 0.13 
                 No 
                 No 
               
               
                 G589Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.01 
                 0.41 
                 Yes 
                 No 
               
               
                 G589V 
                 −0.65 
                 0.05 
                 −0.97 
                 0.06 
                 −0.22 
                 0.13 
                 No 
                 No 
               
               
                 F590A 
                 −0.43 
                 0.05 
                 −1.38 
                 0.07 
                 −1.07 
                 0.15 
                 No 
                 No 
               
               
                 F590R 
                 −0.22 
                 0.05 
                 −0.83 
                 0.05 
                 −0.62 
                 0.15 
                 No 
                 No 
               
               
                 F590N 
                 −0.95 
                 0.17 
                 −0.65 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F590C 
                 −0.49 
                 0.08 
                 −0.73 
                 0.08 
                 −1.06 
                 0.20 
                 No 
                 No 
               
               
                 F590E 
                 −1.00 
                 0.09 
                 −1.26 
                 0.10 
                 −0.44 
                 0.26 
                 No 
                 No 
               
               
                 F590G 
                 −1.05 
                 0.04 
                 −1.44 
                 0.05 
                 −1.47 
                 0.09 
                 No 
                 No 
               
               
                 F590I 
                 0.01 
                 0.09 
                 0.10 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F590L 
                 −0.02 
                 0.04 
                 −0.21 
                 0.04 
                 −0.51 
                 0.06 
                 No 
                 No 
               
               
                 F590M 
                 −0.27 
                 0.12 
                 −0.41 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F590P 
                 −1.08 
                 0.10 
                 −1.31 
                 0.10 
                 −1.37 
                 0.17 
                 No 
                 No 
               
               
                 F590S 
                 −0.03 
                 0.05 
                 −0.29 
                 0.05 
                 −0.61 
                 0.07 
                 No 
                 No 
               
               
                 F590T 
                 −1.50 
                 0.15 
                 −1.08 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F590W 
                 0.04 
                 0.07 
                 −0.11 
                 0.07 
                 −0.87 
                 0.26 
                 Yes 
                 No 
               
               
                 F590Y 
                 0.07 
                 0.06 
                 −0.18 
                 0.07 
                 −0.19 
                 0.17 
                 Yes 
                 No 
               
               
                 F590V 
                 −1.03 
                 0.06 
                 −0.97 
                 0.06 
                 −0.98 
                 0.14 
                 No 
                 No 
               
               
                 D591A 
                 0.20 
                 0.04 
                 0.07 
                 0.04 
                 −0.54 
                 0.05 
                 Yes 
                 No 
               
               
                 D591R 
                 −0.94 
                 0.05 
                 −1.06 
                 0.05 
                 −0.45 
                 0.13 
                 No 
                 No 
               
               
                 D591N 
                 −0.49 
                 0.10 
                 −0.61 
                 0.10 
                 −0.54 
                 0.14 
                 No 
                 No 
               
               
                 D591C 
                 −0.66 
                 0.10 
                 −0.68 
                 0.09 
                 −0.47 
                 0.23 
                 No 
                 No 
               
               
                 D591Q 
                 −0.34 
                 0.10 
                 0.11 
                 0.09 
                 −0.15 
                 0.38 
                 Yes 
                 No 
               
               
                 D591E 
                 −0.43 
                 0.05 
                 −0.39 
                 0.05 
                 −0.84 
                 0.14 
                 No 
                 No 
               
               
                 D591G 
                 −0.62 
                 0.03 
                 −0.81 
                 0.03 
                 −0.59 
                 0.03 
                 No 
                 No 
               
               
                 D591H 
                 −1.19 
                 0.16 
                 −0.84 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D591L 
                 −0.17 
                 0.06 
                 −0.59 
                 0.07 
                 −0.99 
                 0.20 
                 No 
                 No 
               
               
                 D591K 
                 −0.51 
                 0.12 
                 −0.27 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D591M 
                 −0.90 
                 0.12 
                 −0.93 
                 0.12 
                 −0.36 
                 0.27 
                 No 
                 No 
               
               
                 D591S 
                 −0.69 
                 0.07 
                 −1.41 
                 0.09 
                 −0.67 
                 0.17 
                 No 
                 No 
               
               
                 D591T 
                 −0.15 
                 0.08 
                 −0.93 
                 0.10 
                 −1.04 
                 0.23 
                 No 
                 No 
               
               
                 D591W 
                 −1.02 
                 0.08 
                 −0.91 
                 0.07 
                 −0.42 
                 0.16 
                 No 
                 No 
               
               
                 D591Y 
                 0.08 
                 0.10 
                 −0.62 
                 0.12 
                 −0.50 
                 0.17 
                 Yes 
                 No 
               
               
                 D591V 
                 −0.76 
                 0.05 
                 −1.11 
                 0.05 
                 −1.12 
                 0.11 
                 No 
                 No 
               
               
                 K592A 
                 −1.60 
                 0.09 
                 −0.60 
                 0.06 
                 −1.42 
                 0.15 
                 No 
                 No 
               
               
                 K592R 
                 −0.98 
                 0.05 
                 −0.77 
                 0.04 
                 −1.03 
                 0.05 
                 No 
                 No 
               
               
                 K592N 
                 −0.12 
                 0.10 
                 0.07 
                 0.10 
                 −0.91 
                 0.19 
                 Yes 
                 No 
               
               
                 K592Q 
                 −0.52 
                 0.07 
                 −0.77 
                 0.08 
                 −0.30 
                 0.10 
                 No 
                 No 
               
               
                 K592E 
                 −0.52 
                 0.07 
                 −0.76 
                 0.07 
                 −1.22 
                 0.10 
                 No 
                 No 
               
               
                 K592G 
                 −1.76 
                 0.06 
                 −1.45 
                 0.05 
                 −1.64 
                 0.08 
                 No 
                 No 
               
               
                 K592L 
                 −1.72 
                 0.08 
                 −1.52 
                 0.08 
                 −1.24 
                 0.13 
                 No 
                 No 
               
               
                 K592M 
                 −0.70 
                 0.07 
                 −0.58 
                 0.07 
                 −0.68 
                 0.07 
                 No 
                 No 
               
               
                 K592P 
                 −1.70 
                 0.14 
                 −1.63 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K592S 
                 −1.67 
                 0.10 
                 −1.56 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K592* 
                 0.00 
                 0.08 
                 −1.63 
                 0.13 
                 −0.91 
                 0.18 
                 Yes 
                 No 
               
               
                 K592T 
                 −1.38 
                 0.11 
                 −0.98 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K592W 
                 −1.60 
                 0.10 
                 −1.14 
                 0.08 
                 −0.21 
                 0.20 
                 No 
                 No 
               
               
                 K592V 
                 −1.60 
                 0.06 
                 −1.14 
                 0.05 
                 −1.90 
                 0.08 
                 No 
                 No 
               
               
                 M593A 
                 −1.94 
                 0.07 
                 −1.00 
                 0.05 
                 −1.73 
                 0.06 
                 No 
                 No 
               
               
                 M593R 
                 −0.79 
                 0.03 
                 −0.81 
                 0.03 
                 −0.81 
                 0.03 
                 No 
                 No 
               
               
                 M593N 
                 −1.58 
                 0.13 
                 −1.89 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M593D 
                 −2.12 
                 0.13 
                 −1.32 
                 0.09 
                 −1.77 
                 0.18 
                 No 
                 No 
               
               
                 M593C 
                 −0.95 
                 0.07 
                 −0.04 
                 0.06 
                 −1.27 
                 0.10 
                 No 
                 No 
               
               
                 M593Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.83 
                 0.19 
                 Yes 
                 No 
               
               
                 M593E 
                 −2.30 
                 0.10 
                 −2.14 
                 0.09 
                 −1.55 
                 0.14 
                 No 
                 No 
               
               
                 M593G 
                 −1.83 
                 0.04 
                 −1.88 
                 0.04 
                 −1.09 
                 0.07 
                 No 
                 No 
               
               
                 M593I 
                 −0.83 
                 0.07 
                 −1.05 
                 0.08 
                 −1.17 
                 0.12 
                 No 
                 No 
               
               
                 M593L 
                 −0.10 
                 0.03 
                 −0.33 
                 0.03 
                 −0.52 
                 0.06 
                 No 
                 No 
               
               
                 M593K 
                 −1.64 
                 0.09 
                 −1.56 
                 0.08 
                 −1.09 
                 0.05 
                 No 
                 No 
               
               
                 M593F 
                 −1.98 
                 0.12 
                 −0.83 
                 0.08 
                 −1.61 
                 0.12 
                 No 
                 No 
               
               
                 M593P 
                 −1.56 
                 0.10 
                 −2.23 
                 0.12 
                 −0.38 
                 0.12 
                 No 
                 No 
               
               
                 M593S 
                 −1.58 
                 0.06 
                 −1.88 
                 0.07 
                 −1.33 
                 0.11 
                 No 
                 No 
               
               
                 M593* 
                 −2.27 
                 0.12 
                 −2.28 
                 0.12 
                 −1.55 
                 0.18 
                 No 
                 No 
               
               
                 M593T 
                 −1.01 
                 0.06 
                 −0.79 
                 0.05 
                 −0.64 
                 0.10 
                 No 
                 No 
               
               
                 M593W 
                 −0.92 
                 0.05 
                 −1.57 
                 0.07 
                 −2.41 
                 0.16 
                 No 
                 No 
               
               
                 M593V 
                 −0.56 
                 0.03 
                 −1.41 
                 0.04 
                 −1.07 
                 0.07 
                 No 
                 No 
               
               
                 Y594A 
                 −0.40 
                 0.04 
                 −1.29 
                 0.05 
                 −1.34 
                 0.10 
                 No 
                 No 
               
               
                 Y594R 
                 −0.02 
                 0.03 
                 −0.18 
                 0.03 
                 −1.14 
                 0.08 
                 No 
                 No 
               
               
                 Y594N 
                 −1.08 
                 0.10 
                 −0.80 
                 0.08 
                 −0.62 
                 0.15 
                 No 
                 No 
               
               
                 Y594D 
                 −1.17 
                 0.07 
                 −1.36 
                 0.07 
                 −1.43 
                 0.13 
                 No 
                 No 
               
               
                 Y594C 
                 −0.47 
                 0.06 
                 −0.08 
                 0.06 
                 −1.45 
                 0.10 
                 No 
                 No 
               
               
                 Y594Q 
                 −1.06 
                 0.08 
                 −0.26 
                 0.06 
                 −1.14 
                 0.12 
                 No 
                 No 
               
               
                 Y594E 
                 −0.42 
                 0.04 
                 −0.82 
                 0.05 
                 −2.58 
                 0.11 
                 No 
                 No 
               
               
                 Y594G 
                 −1.21 
                 0.03 
                 −1.58 
                 0.03 
                 −1.51 
                 0.04 
                 No 
                 No 
               
               
                 Y594H 
                 0.04 
                 0.07 
                 −0.11 
                 0.07 
                 −0.42 
                 0.12 
                 Yes 
                 No 
               
               
                 Y594I 
                 −0.73 
                 0.10 
                 −0.78 
                 0.10 
                 −0.74 
                 0.27 
                 No 
                 No 
               
               
                 Y594L 
                 −0.88 
                 0.05 
                 −0.67 
                 0.04 
                 −1.45 
                 0.10 
                 No 
                 No 
               
               
                 Y594K 
                 −0.40 
                 0.06 
                 −0.88 
                 0.07 
                 −1.41 
                 0.17 
                 No 
                 No 
               
               
                 Y594M 
                 0.05 
                 0.06 
                 −0.76 
                 0.07 
                 −1.47 
                 0.18 
                 Yes 
                 No 
               
               
                 Y594F 
                 −0.18 
                 0.07 
                 −0.07 
                 0.06 
                 −0.45 
                 0.14 
                 No 
                 No 
               
               
                 Y594S 
                 −1.00 
                 0.05 
                 −0.88 
                 0.05 
                 −1.40 
                 0.06 
                 No 
                 No 
               
               
                 Y594* 
                 −1.41 
                 0.08 
                 −0.73 
                 0.06 
                 −1.67 
                 0.13 
                 No 
                 No 
               
               
                 Y594T 
                 −1.66 
                 0.09 
                 −1.71 
                 0.09 
                 −1.37 
                 0.15 
                 No 
                 No 
               
               
                 Y594W 
                 −0.33 
                 0.04 
                 −0.93 
                 0.05 
                 −1.06 
                 0.10 
                 No 
                 No 
               
               
                 Y594V 
                 −0.40 
                 0.04 
                 −0.47 
                 0.04 
                 −0.96 
                 0.08 
                 No 
                 No 
               
               
                 Y595A 
                 −1.63 
                 0.05 
                 −1.08 
                 0.04 
                 −2.32 
                 0.10 
                 No 
                 No 
               
               
                 Y595R 
                 −1.29 
                 0.04 
                 −1.66 
                 0.05 
                 −2.00 
                 0.06 
                 No 
                 No 
               
               
                 Y595N 
                 −1.61 
                 0.14 
                 −0.78 
                 0.10 
                 −0.80 
                 0.19 
                 No 
                 No 
               
               
                 Y595D 
                 −1.27 
                 0.09 
                 −1.50 
                 0.09 
                 −1.84 
                 0.06 
                 No 
                 No 
               
               
                 Y595C 
                 −0.14 
                 0.05 
                 −0.50 
                 0.05 
                 −1.06 
                 0.11 
                 No 
                 No 
               
               
                 Y595Q 
                 −1.71 
                 0.10 
                 −1.18 
                 0.08 
                 −1.13 
                 0.22 
                 No 
                 No 
               
               
                 Y595E 
                 −2.05 
                 0.08 
                 −2.21 
                 0.08 
                 −2.32 
                 0.03 
                 No 
                 No 
               
               
                 Y595G 
                 −1.67 
                 0.03 
                 −1.31 
                 0.03 
                 −1.77 
                 0.03 
                 No 
                 No 
               
               
                 Y595H 
                 −0.86 
                 0.09 
                 −0.57 
                 0.08 
                 −0.77 
                 0.13 
                 No 
                 No 
               
               
                 Y595I 
                 −1.20 
                 0.14 
                 −1.49 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y595L 
                 −0.09 
                 0.04 
                 0.08 
                 0.04 
                 −0.83 
                 0.12 
                 Yes 
                 No 
               
               
                 Y595K 
                 −1.17 
                 0.09 
                 −1.74 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y595M 
                 0.24 
                 0.06 
                 −0.10 
                 0.07 
                 −0.34 
                 0.19 
                 Yes 
                 No 
               
               
                 Y595F 
                 −1.21 
                 0.09 
                 −0.70 
                 0.08 
                 −1.09 
                 0.14 
                 No 
                 No 
               
               
                 Y595S 
                 −1.31 
                 0.05 
                 −1.19 
                 0.05 
                 −1.64 
                 0.09 
                 No 
                 No 
               
               
                 Y595* 
                 −1.32 
                 0.07 
                 −1.52 
                 0.08 
                 −1.60 
                 0.09 
                 No 
                 No 
               
               
                 Y595T 
                 −0.27 
                 0.05 
                 −0.81 
                 0.06 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y595W 
                 −1.72 
                 0.06 
                 −1.71 
                 0.06 
                 −1.97 
                 0.10 
                 No 
                 No 
               
               
                 Y595V 
                 −0.32 
                 0.03 
                 −0.74 
                 0.04 
                 −2.00 
                 0.06 
                 No 
                 No 
               
               
                 D596E 
                 0.04 
                 0.04 
                 0.24 
                 0.04 
                 0.69 
                 0.05 
                 Yes 
                 Yes 
               
               
                 D596A 
                 0.07 
                 0.03 
                 −0.18 
                 0.04 
                 −0.99 
                 0.09 
                 Yes 
                 No 
               
               
                 D596R 
                 0.01 
                 0.03 
                 0.07 
                 0.03 
                 −0.20 
                 0.04 
                 Yes 
                 No 
               
               
                 D596N 
                 −0.12 
                 0.08 
                 0.29 
                 0.08 
                 0.39 
                 0.15 
                 Yes 
                 No 
               
               
                 D596C 
                 −0.01 
                 0.07 
                 −0.24 
                 0.07 
                 −0.55 
                 0.06 
                 No 
                 No 
               
               
                 D596Q 
                 −0.04 
                 0.09 
                 0.42 
                 0.08 
                 0.46 
                 0.31 
                 Yes 
                 No 
               
               
                 D596G 
                 −0.23 
                 0.02 
                 −0.22 
                 0.02 
                 −1.16 
                 0.05 
                 No 
                 No 
               
               
                 D596H 
                 0.24 
                 0.10 
                 −0.18 
                 0.11 
                 0.16 
                 0.26 
                 Yes 
                 No 
               
               
                 D596L 
                 −0.92 
                 0.07 
                 −0.10 
                 0.05 
                 −0.75 
                 0.18 
                 No 
                 No 
               
               
                 D596K 
                 0.01 
                 0.08 
                 0.36 
                 0.07 
                 −0.07 
                 0.19 
                 Yes 
                 No 
               
               
                 D596M 
                 0.26 
                 0.08 
                 0.29 
                 0.07 
                 −0.27 
                 0.28 
                 Yes 
                 No 
               
               
                 D596F 
                 0.03 
                 0.11 
                 −0.55 
                 0.13 
                 0.09 
                 0.13 
                 Yes 
                 No 
               
               
                 D596P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.56 
                 0.24 
                 Yes 
                 No 
               
               
                 D596S 
                 −0.58 
                 0.06 
                 −0.29 
                 0.05 
                 0.37 
                 0.07 
                 Yes 
                 No 
               
               
                 D596* 
                 −0.99 
                 0.11 
                 −1.29 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D596T 
                 −1.56 
                 0.12 
                 0.65 
                 0.06 
                 −1.10 
                 0.23 
                 Yes 
                 No 
               
               
                 D596W 
                 −0.19 
                 0.05 
                 0.12 
                 0.05 
                 −1.34 
                 0.11 
                 Yes 
                 No 
               
               
                 D596Y 
                 −0.55 
                 0.09 
                 −0.32 
                 0.08 
                 −0.27 
                 0.16 
                 No 
                 No 
               
               
                 D596V 
                 −0.06 
                 0.03 
                 −0.22 
                 0.03 
                 −1.39 
                 0.08 
                 No 
                 No 
               
               
                 Y597A 
                 −2.00 
                 0.06 
                 −1.33 
                 0.05 
                 −2.10 
                 0.12 
                 No 
                 No 
               
               
                 Y597R 
                 −2.18 
                 0.05 
                 −2.13 
                 0.05 
                 −2.18 
                 0.04 
                 No 
                 No 
               
               
                 Y597N 
                 −1.28 
                 0.11 
                 −0.66 
                 0.09 
                 −1.35 
                 0.13 
                 No 
                 No 
               
               
                 Y597D 
                 −0.30 
                 0.03 
                 −0.28 
                 0.03 
                 −0.34 
                 0.04 
                 No 
                 No 
               
               
                 Y597C 
                 −0.79 
                 0.06 
                 −1.14 
                 0.07 
                 −1.47 
                 0.05 
                 No 
                 No 
               
               
                 Y597E 
                 −2.33 
                 0.09 
                 −2.41 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y597G 
                 −1.89 
                 0.04 
                 −2.15 
                 0.04 
                 −1.96 
                 0.05 
                 No 
                 No 
               
               
                 Y597H 
                 −0.45 
                 0.07 
                 −0.25 
                 0.06 
                 −0.71 
                 0.10 
                 No 
                 No 
               
               
                 Y597I 
                 −0.51 
                 0.11 
                 −1.26 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y597L 
                 0.24 
                 0.04 
                 0.32 
                 0.04 
                 −0.31 
                 0.09 
                 Yes 
                 No 
               
               
                 Y597M 
                 −0.11 
                 0.07 
                 −1.15 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y597F 
                 −0.08 
                 0.07 
                 −0.16 
                 0.07 
                 0.56 
                 0.06 
                 Yes 
                 No 
               
               
                 Y597P 
                 −2.03 
                 0.11 
                 −2.30 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y597S 
                 −1.25 
                 0.05 
                 −1.04 
                 0.05 
                 −2.00 
                 0.09 
                 No 
                 No 
               
               
                 Y597* 
                 −0.94 
                 0.06 
                 −0.96 
                 0.06 
                 −2.02 
                 0.13 
                 No 
                 No 
               
               
                 Y597T 
                 −1.78 
                 0.09 
                 −2.62 
                 0.12 
                 −1.94 
                 0.04 
                 No 
                 No 
               
               
                 Y597W 
                 −1.16 
                 0.05 
                 −1.33 
                 0.05 
                 −2.30 
                 0.08 
                 No 
                 No 
               
               
                 Y597V 
                 −1.95 
                 0.07 
                 −1.63 
                 0.06 
                 −2.69 
                 0.08 
                 No 
                 No 
               
               
                 F598A 
                 −1.68 
                 0.07 
                 −1.98 
                 0.08 
                 −2.09 
                 0.12 
                 No 
                 No 
               
               
                 F598R 
                 −1.81 
                 0.06 
                 −2.21 
                 0.07 
                 −1.57 
                 0.11 
                 No 
                 No 
               
               
                 F598C 
                 −1.96 
                 0.12 
                 −2.25 
                 0.13 
                 −1.21 
                 0.15 
                 No 
                 No 
               
               
                 F598G 
                 −2.06 
                 0.05 
                 −1.79 
                 0.04 
                 −0.96 
                 0.03 
                 No 
                 No 
               
               
                 F598I 
                 −0.32 
                 0.09 
                 −0.44 
                 0.09 
                 −0.75 
                 0.12 
                 No 
                 No 
               
               
                 F598L 
                 −0.25 
                 0.04 
                 −0.09 
                 0.04 
                 −0.65 
                 0.04 
                 No 
                 No 
               
               
                 F598M 
                 −0.35 
                 0.09 
                 −0.55 
                 0.09 
                 −0.87 
                 0.27 
                 No 
                 No 
               
               
                 F598P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.93 
                 0.07 
                 Yes 
                 No 
               
               
                 F598S 
                 −1.12 
                 0.06 
                 −1.33 
                 0.06 
                 −1.35 
                 0.08 
                 No 
                 No 
               
               
                 F598W 
                 −1.23 
                 0.06 
                 −0.34 
                 0.05 
                 −1.74 
                 0.12 
                 No 
                 No 
               
               
                 F598Y 
                 −0.52 
                 0.09 
                 −0.44 
                 0.09 
                 −0.60 
                 0.15 
                 No 
                 No 
               
               
                 F598V 
                 −1.37 
                 0.06 
                 −1.39 
                 0.05 
                 −2.25 
                 0.09 
                 No 
                 No 
               
               
                 P599G 
                 0.84 
                 0.04 
                 0.83 
                 0.04 
                 1.01 
                 0.05 
                 Yes 
                 Yes 
               
               
                 P599A 
                 −1.03 
                 0.07 
                 −0.85 
                 0.06 
                 −1.42 
                 0.11 
                 No 
                 No 
               
               
                 P599R 
                 −1.89 
                 0.09 
                 −1.20 
                 0.06 
                 −2.08 
                 0.14 
                 No 
                 No 
               
               
                 P599N 
                 −0.66 
                 0.16 
                 −0.33 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P599E 
                 −2.04 
                 0.15 
                 −2.07 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P599H 
                 −1.01 
                 0.14 
                 −0.99 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P599L 
                 −1.56 
                 0.09 
                 −1.36 
                 0.08 
                 −1.46 
                 0.11 
                 No 
                 No 
               
               
                 P599S 
                 −0.09 
                 0.03 
                 −0.10 
                 0.03 
                 −0.56 
                 0.04 
                 No 
                 No 
               
               
                 P599* 
                 −1.14 
                 0.13 
                 −1.42 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P599T 
                 −0.42 
                 0.07 
                 −0.95 
                 0.08 
                 −1.37 
                 0.14 
                 No 
                 No 
               
               
                 P599V 
                 −1.88 
                 0.12 
                 −1.85 
                 0.11 
                 −1.81 
                 0.14 
                 No 
                 No 
               
               
                 D600A 
                 0.43 
                 0.06 
                 −0.31 
                 0.07 
                 0.68 
                 0.14 
                 Yes 
                 No 
               
               
                 D600R 
                 −0.88 
                 0.07 
                 −0.40 
                 0.06 
                 −1.67 
                 0.19 
                 No 
                 No 
               
               
                 D600N 
                 −0.03 
                 0.07 
                 −0.16 
                 0.07 
                 0.67 
                 0.14 
                 Yes 
                 No 
               
               
                 D600C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.32 
                 0.48 
                 Yes 
                 No 
               
               
                 D600Q 
                 −0.37 
                 0.15 
                 −0.01 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D600E 
                 −0.44 
                 0.07 
                 −0.46 
                 0.07 
                 −0.95 
                 0.22 
                 No 
                 No 
               
               
                 D600G 
                 −0.19 
                 0.04 
                 −0.33 
                 0.04 
                 1.07 
                 0.05 
                 Yes 
                 No 
               
               
                 D600H 
                 −0.08 
                 0.13 
                 −0.54 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D600L 
                 −1.26 
                 0.13 
                 −1.19 
                 0.12 
                 −0.50 
                 0.29 
                 No 
                 No 
               
               
                 D600P 
                 −0.14 
                 0.11 
                 −1.46 
                 0.16 
                 0.47 
                 0.45 
                 Yes 
                 No 
               
               
                 D600S 
                 0.86 
                 0.07 
                 −0.03 
                 0.08 
                 0.74 
                 0.14 
                 Yes 
                 No 
               
               
                 D600T 
                 −1.42 
                 0.15 
                 −0.70 
                 0.12 
                 0.43 
                 0.29 
                 Yes 
                 No 
               
               
                 D600W 
                 −0.67 
                 0.11 
                 −0.51 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D600Y 
                 −0.29 
                 0.13 
                 −0.19 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D600V 
                 −0.05 
                 0.06 
                 −0.23 
                 0.06 
                 −0.56 
                 0.13 
                 No 
                 No 
               
               
                 A601R 
                 −1.65 
                 0.07 
                 −1.62 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A601D 
                 −1.38 
                 0.13 
                 −1.10 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A601C 
                 0.26 
                 0.08 
                 0.26 
                 0.08 
                 −0.25 
                 0.24 
                 Yes 
                 No 
               
               
                 A601G 
                 −1.05 
                 0.04 
                 −0.63 
                 0.04 
                 −1.44 
                 0.04 
                 No 
                 No 
               
               
                 A601L 
                 −2.16 
                 0.13 
                 −1.44 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A601P 
                 −1.40 
                 0.13 
                 −1.20 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A601S 
                 −0.60 
                 0.06 
                 0.23 
                 0.04 
                 −0.52 
                 0.08 
                 Yes 
                 No 
               
               
                 A601T 
                 −0.84 
                 0.08 
                 −0.53 
                 0.07 
                 −0.99 
                 0.12 
                 No 
                 No 
               
               
                 A601W 
                 −1.89 
                 0.12 
                 −1.84 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A601V 
                 −0.48 
                 0.05 
                 −0.23 
                 0.04 
                 −0.77 
                 0.06 
                 No 
                 No 
               
               
                 A602C 
                 0.64 
                 0.09 
                 0.61 
                 0.09 
                 0.73 
                 0.28 
                 Yes 
                 Yes 
               
               
                 A602R 
                 −0.59 
                 0.07 
                 −0.97 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A602D 
                 0.04 
                 0.04 
                 −0.09 
                 0.04 
                 −0.40 
                 0.05 
                 Yes 
                 No 
               
               
                 A602G 
                 −0.52 
                 0.05 
                 −0.56 
                 0.05 
                 −1.62 
                 0.06 
                 No 
                 No 
               
               
                 A602H 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.37 
                 0.35 
                 Yes 
                 No 
               
               
                 A602L 
                 −1.97 
                 0.14 
                 −1.06 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A602P 
                 −0.80 
                 0.09 
                 −0.42 
                 0.08 
                 −0.71 
                 0.15 
                 No 
                 No 
               
               
                 A602S 
                 −0.38 
                 0.07 
                 −0.14 
                 0.06 
                 −0.73 
                 0.16 
                 No 
                 No 
               
               
                 A602T 
                 −0.28 
                 0.06 
                 −0.03 
                 0.06 
                 −0.51 
                 0.11 
                 No 
                 No 
               
               
                 A602W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.89 
                 0.37 
                 Yes 
                 No 
               
               
                 A602V 
                 −0.77 
                 0.06 
                 −0.66 
                 0.05 
                 −1.41 
                 0.10 
                 No 
                 No 
               
               
                 K603A 
                 −1.34 
                 0.07 
                 −1.59 
                 0.07 
                 −1.76 
                 0.05 
                 No 
                 No 
               
               
                 K603R 
                 −0.56 
                 0.04 
                 −0.37 
                 0.03 
                 −0.46 
                 0.04 
                 No 
                 No 
               
               
                 K603N 
                 −1.59 
                 0.16 
                 −1.11 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K603C 
                 −1.03 
                 0.10 
                 −1.23 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K603Q 
                 −1.30 
                 0.11 
                 −1.57 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K603E 
                 −1.40 
                 0.07 
                 −0.68 
                 0.05 
                 −1.60 
                 0.10 
                 No 
                 No 
               
               
                 K603G 
                 −1.88 
                 0.05 
                 −1.70 
                 0.04 
                 −1.97 
                 0.08 
                 No 
                 No 
               
               
                 K603H 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.51 
                 0.41 
                 Yes 
                 No 
               
               
                 K603L 
                 −0.77 
                 0.06 
                 −0.60 
                 0.06 
                 −1.63 
                 0.14 
                 No 
                 No 
               
               
                 K603M 
                 0.00 
                 0.06 
                 −0.57 
                 0.07 
                 −1.02 
                 0.11 
                 No 
                 No 
               
               
                 K603P 
                 −1.70 
                 0.12 
                 −1.06 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K603S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −2.06 
                 0.05 
                 Yes 
                 No 
               
               
                 K603* 
                 −1.20 
                 0.09 
                 −1.66 
                 0.11 
                 −1.37 
                 0.16 
                 No 
                 No 
               
               
                 K603T 
                 −1.11 
                 0.08 
                 −1.15 
                 0.08 
                 −1.13 
                 0.13 
                 No 
                 No 
               
               
                 K603W 
                 −2.79 
                 0.14 
                 −1.74 
                 0.09 
                 −1.45 
                 0.14 
                 No 
                 No 
               
               
                 K603V 
                 −1.72 
                 0.07 
                 −1.54 
                 0.06 
                 −2.40 
                 0.07 
                 No 
                 No 
               
               
                 M604A 
                 −2.19 
                 0.15 
                 −1.92 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M604R 
                 −0.96 
                 0.06 
                 −1.76 
                 0.08 
                 −2.02 
                 0.13 
                 No 
                 No 
               
               
                 M604G 
                 −2.12 
                 0.08 
                 −0.82 
                 0.05 
                 −1.81 
                 0.12 
                 No 
                 No 
               
               
                 M604I 
                 −0.58 
                 0.10 
                 −0.71 
                 0.10 
                 −0.51 
                 0.15 
                 No 
                 No 
               
               
                 M604L 
                 −0.74 
                 0.06 
                 −0.50 
                 0.06 
                 −0.25 
                 0.06 
                 No 
                 No 
               
               
                 M604K 
                 −1.08 
                 0.15 
                 −0.78 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M604T 
                 −0.14 
                 0.06 
                 0.01 
                 0.06 
                 −0.44 
                 0.09 
                 Yes 
                 No 
               
               
                 M604W 
                 −1.97 
                 0.14 
                 −2.03 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 M604V 
                 −1.38 
                 0.08 
                 −1.32 
                 0.07 
                 −1.38 
                 0.09 
                 No 
                 No 
               
               
                 I605A 
                 −1.32 
                 0.09 
                 −1.04 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605R 
                 −2.07 
                 0.09 
                 −2.36 
                 0.10 
                 −2.12 
                 0.15 
                 No 
                 No 
               
               
                 I605N 
                 −0.93 
                 0.10 
                 −0.19 
                 0.08 
                 −0.76 
                 0.16 
                 No 
                 No 
               
               
                 I605C 
                 0.20 
                 0.09 
                 −0.98 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605G 
                 −1.69 
                 0.07 
                 −1.41 
                 0.06 
                 −2.04 
                 0.14 
                 No 
                 No 
               
               
                 I605L 
                 −0.93 
                 0.07 
                 −0.25 
                 0.06 
                 −1.49 
                 0.14 
                 No 
                 No 
               
               
                 I605M 
                 −1.09 
                 0.09 
                 −0.86 
                 0.08 
                 −1.44 
                 0.15 
                 No 
                 No 
               
               
                 I605F 
                 −0.50 
                 0.11 
                 −0.52 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605S 
                 −1.91 
                 0.11 
                 −1.82 
                 0.10 
                 −1.55 
                 0.10 
                 No 
                 No 
               
               
                 I605T 
                 −0.45 
                 0.07 
                 −0.67 
                 0.07 
                 −1.09 
                 0.12 
                 No 
                 No 
               
               
                 I605V 
                 0.13 
                 0.05 
                 −0.04 
                 0.05 
                 −0.33 
                 0.11 
                 Yes 
                 No 
               
               
                 I605A 
                 −1.42 
                 0.10 
                 −0.82 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605R 
                 −2.12 
                 0.09 
                 −2.15 
                 0.10 
                 −1.82 
                 0.16 
                 No 
                 No 
               
               
                 I605N 
                 0.04 
                 0.06 
                 0.36 
                 0.06 
                 −0.41 
                 0.09 
                 Yes 
                 No 
               
               
                 I605D 
                 −1.00 
                 0.09 
                 −0.60 
                 0.08 
                 −0.72 
                 0.14 
                 No 
                 No 
               
               
                 I605C 
                 0.10 
                 0.10 
                 −0.82 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605G 
                 −1.69 
                 0.07 
                 −1.23 
                 0.06 
                 −1.96 
                 0.13 
                 No 
                 No 
               
               
                 I605L 
                 −0.10 
                 0.03 
                 0.14 
                 0.03 
                 −1.00 
                 0.08 
                 Yes 
                 No 
               
               
                 I605M 
                 −0.89 
                 0.09 
                 −0.63 
                 0.08 
                 −1.25 
                 0.21 
                 No 
                 No 
               
               
                 I605F 
                 −0.55 
                 0.10 
                 −0.33 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I605S 
                 −0.22 
                 0.04 
                 0.10 
                 0.04 
                 −1.29 
                 0.08 
                 Yes 
                 No 
               
               
                 I605T 
                 −0.02 
                 0.04 
                 0.21 
                 0.04 
                 −0.53 
                 0.07 
                 Yes 
                 No 
               
               
                 I605V 
                 0.19 
                 0.05 
                 0.25 
                 0.05 
                 −0.06 
                 0.10 
                 Yes 
                 No 
               
               
                 P606A 
                 −1.59 
                 0.10 
                 −2.27 
                 0.12 
                 −1.25 
                 0.17 
                 No 
                 No 
               
               
                 P606R 
                 −1.77 
                 0.08 
                 −2.62 
                 0.12 
                 −1.94 
                 0.15 
                 No 
                 No 
               
               
                 P606G 
                 −1.63 
                 0.07 
                 −2.12 
                 0.08 
                 −1.89 
                 0.14 
                 No 
                 No 
               
               
                 P606H 
                 −0.89 
                 0.13 
                 −0.93 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P606L 
                 −0.77 
                 0.07 
                 −1.12 
                 0.08 
                 −1.30 
                 0.15 
                 No 
                 No 
               
               
                 P606S 
                 −1.42 
                 0.10 
                 −1.22 
                 0.09 
                 −1.16 
                 0.14 
                 No 
                 No 
               
               
                 P606T 
                 −0.06 
                 0.06 
                 −0.63 
                 0.07 
                 −0.40 
                 0.08 
                 No 
                 No 
               
               
                 P606W 
                 −0.88 
                 0.11 
                 −1.05 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P606V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.59 
                 0.24 
                 Yes 
                 No 
               
               
                 P606A 
                 −1.59 
                 0.10 
                 −2.27 
                 0.14 
                 −1.33 
                 0.19 
                 No 
                 No 
               
               
                 P606R 
                 −1.77 
                 0.09 
                 −1.59 
                 0.08 
                 −1.76 
                 0.15 
                 No 
                 No 
               
               
                 P606Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.43 
                 0.12 
                 Yes 
                 No 
               
               
                 P606G 
                 −1.73 
                 0.08 
                 −2.00 
                 0.09 
                 −1.79 
                 0.16 
                 No 
                 No 
               
               
                 P606H 
                 0.13 
                 0.07 
                 0.17 
                 0.07 
                 −0.14 
                 0.04 
                 Yes 
                 No 
               
               
                 P606L 
                 −0.98 
                 0.08 
                 −1.23 
                 0.09 
                 −1.00 
                 0.16 
                 No 
                 No 
               
               
                 P606S 
                 −1.64 
                 0.12 
                 −1.35 
                 0.11 
                 −1.37 
                 0.17 
                 No 
                 No 
               
               
                 P606T 
                 −0.10 
                 0.07 
                 −0.63 
                 0.08 
                 −0.65 
                 0.11 
                 No 
                 No 
               
               
                 P606W 
                 −1.06 
                 0.12 
                 −0.93 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P606V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.33 
                 0.27 
                 Yes 
                 No 
               
               
                 K607A 
                 −1.61 
                 0.05 
                 −1.70 
                 0.06 
                 −2.05 
                 0.10 
                 No 
                 No 
               
               
                 K607R 
                 −1.65 
                 0.04 
                 −1.32 
                 0.03 
                 −2.05 
                 0.03 
                 No 
                 No 
               
               
                 K607N 
                 −0.51 
                 0.07 
                 −0.19 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K607D 
                 −2.48 
                 0.14 
                 −1.83 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K607C 
                 −1.09 
                 0.07 
                 −1.20 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K607Q 
                 −1.77 
                 0.09 
                 −1.64 
                 0.09 
                 −1.87 
                 0.13 
                 No 
                 No 
               
               
                 K607E 
                 −1.93 
                 0.06 
                 −1.40 
                 0.05 
                 −1.61 
                 0.07 
                 No 
                 No 
               
               
                 K607G 
                 −1.81 
                 0.03 
                 −1.60 
                 0.03 
                 −1.79 
                 0.03 
                 No 
                 No 
               
               
                 K607H 
                 −1.16 
                 0.12 
                 −0.39 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K607L 
                 −1.08 
                 0.05 
                 −1.66 
                 0.06 
                 −1.63 
                 0.08 
                 No 
                 No 
               
               
                 K607M 
                 −0.42 
                 0.06 
                 −1.47 
                 0.08 
                 −0.97 
                 0.05 
                 No 
                 No 
               
               
                 K607F 
                 −1.55 
                 0.12 
                 −1.20 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K607P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.84 
                 0.14 
                 Yes 
                 No 
               
               
                 K607S 
                 −1.89 
                 0.06 
                 −1.43 
                 0.06 
                 −1.53 
                 0.04 
                 No 
                 No 
               
               
                 K607* 
                 −1.44 
                 0.07 
                 −0.97 
                 0.06 
                 −1.20 
                 0.14 
                 No 
                 No 
               
               
                 K607T 
                 −2.23 
                 0.09 
                 −1.26 
                 0.06 
                 −1.98 
                 0.11 
                 No 
                 No 
               
               
                 K607W 
                 −1.92 
                 0.06 
                 −1.88 
                 0.06 
                 −1.81 
                 0.10 
                 No 
                 No 
               
               
                 K607V 
                 −1.80 
                 0.05 
                 −1.85 
                 0.06 
                 −1.86 
                 0.03 
                 No 
                 No 
               
               
                 C608A 
                 −1.60 
                 0.09 
                 −1.32 
                 0.08 
                 −1.81 
                 0.15 
                 No 
                 No 
               
               
                 C608R 
                 −0.90 
                 0.04 
                 −0.72 
                 0.04 
                 −1.23 
                 0.09 
                 No 
                 No 
               
               
                 C608E 
                 −1.06 
                 0.09 
                 −1.27 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608G 
                 −1.44 
                 0.05 
                 −0.58 
                 0.04 
                 −1.66 
                 0.09 
                 No 
                 No 
               
               
                 C608L 
                 −1.11 
                 0.08 
                 −0.49 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608F 
                 −1.13 
                 0.12 
                 −0.91 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608P 
                 −1.62 
                 0.14 
                 −1.13 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608S 
                 −0.62 
                 0.05 
                 −0.49 
                 0.05 
                 −1.56 
                 0.12 
                 No 
                 No 
               
               
                 C608* 
                 −1.61 
                 0.13 
                 −0.66 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608W 
                 −1.58 
                 0.09 
                 −1.31 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 C608Y 
                 −0.27 
                 0.06 
                 −0.09 
                 0.06 
                 −0.65 
                 0.15 
                 No 
                 No 
               
               
                 C608V 
                 −1.32 
                 0.07 
                 −2.23 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S609A 
                 0.10 
                 0.07 
                 0.21 
                 0.07 
                 −0.16 
                 0.22 
                 Yes 
                 No 
               
               
                 S609R 
                 −0.60 
                 0.05 
                 −0.45 
                 0.05 
                 −1.32 
                 0.06 
                 No 
                 No 
               
               
                 S609N 
                 −1.18 
                 0.12 
                 −0.49 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S609C 
                 −0.69 
                 0.12 
                 0.21 
                 0.09 
                 −0.27 
                 0.25 
                 Yes 
                 No 
               
               
                 S609G 
                 0.00 
                 0.04 
                 −0.27 
                 0.04 
                 −0.17 
                 0.10 
                 No 
                 No 
               
               
                 S609I 
                 −0.16 
                 0.12 
                 0.43 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S609T 
                 −0.76 
                 0.12 
                 0.55 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S609W 
                 −1.36 
                 0.13 
                 −0.51 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T610A 
                 −0.40 
                 0.05 
                 −0.40 
                 0.05 
                 −0.93 
                 0.09 
                 No 
                 No 
               
               
                 T610R 
                 −1.61 
                 0.07 
                 −0.98 
                 0.06 
                 −1.76 
                 0.15 
                 No 
                 No 
               
               
                 T610N 
                 −0.27 
                 0.10 
                 −0.20 
                 0.10 
                 −0.58 
                 0.12 
                 No 
                 No 
               
               
                 T610C 
                 −0.26 
                 0.09 
                 −0.31 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T610Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.53 
                 0.36 
                 Yes 
                 No 
               
               
                 T610G 
                 −1.36 
                 0.05 
                 −1.25 
                 0.05 
                 −1.62 
                 0.12 
                 No 
                 No 
               
               
                 T610I 
                 −0.82 
                 0.11 
                 −0.98 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T610L 
                 −1.78 
                 0.11 
                 −2.29 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T610P 
                 0.07 
                 0.04 
                 0.33 
                 0.04 
                 −0.62 
                 0.08 
                 Yes 
                 No 
               
               
                 T610S 
                 −0.35 
                 0.06 
                 −0.62 
                 0.06 
                 −0.53 
                 0.07 
                 No 
                 No 
               
               
                 T610V 
                 0.26 
                 0.05 
                 −1.14 
                 0.08 
                 −1.58 
                 0.17 
                 Yes 
                 No 
               
               
                 Q611A 
                 −2.61 
                 0.13 
                 −1.23 
                 0.08 
                 −1.40 
                 0.13 
                 No 
                 No 
               
               
                 Q611R 
                 −0.68 
                 0.04 
                 −0.69 
                 0.04 
                 −1.33 
                 0.04 
                 No 
                 No 
               
               
                 Q611E 
                 −1.22 
                 0.07 
                 −0.58 
                 0.06 
                 −1.18 
                 0.11 
                 No 
                 No 
               
               
                 Q611G 
                 −1.38 
                 0.05 
                 −1.84 
                 0.06 
                 −1.82 
                 0.08 
                 No 
                 No 
               
               
                 Q611H 
                 0.04 
                 0.07 
                 −0.20 
                 0.07 
                 −0.91 
                 0.13 
                 Yes 
                 No 
               
               
                 Q611L 
                 −1.21 
                 0.08 
                 −1.74 
                 0.10 
                 −1.67 
                 0.16 
                 No 
                 No 
               
               
                 Q611K 
                 −0.93 
                 0.09 
                 −0.83 
                 0.09 
                 −1.38 
                 0.16 
                 No 
                 No 
               
               
                 Q611P 
                 0.13 
                 0.06 
                 −0.14 
                 0.06 
                 −0.81 
                 0.08 
                 Yes 
                 No 
               
               
                 Q611S 
                 −2.07 
                 0.11 
                 −0.89 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q611* 
                 −0.75 
                 0.09 
                 −1.11 
                 0.10 
                 −1.17 
                 0.16 
                 No 
                 No 
               
               
                 Q611W 
                 −1.28 
                 0.08 
                 −0.88 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q611V 
                 −1.42 
                 0.07 
                 −1.15 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612M 
                 0.70 
                 0.07 
                 0.70 
                 0.07 
                 0.01 
                 0.03 
                 Yes 
                 Yes 
               
               
                 L612A 
                 −1.32 
                 0.11 
                 −1.11 
                 0.11 
                 −0.98 
                 0.22 
                 No 
                 No 
               
               
                 L612R 
                 0.03 
                 0.05 
                 0.16 
                 0.05 
                 −0.58 
                 0.11 
                 Yes 
                 No 
               
               
                 L612Q 
                 −0.94 
                 0.10 
                 −0.43 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612E 
                 −1.18 
                 0.11 
                 −1.65 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612G 
                 −0.97 
                 0.07 
                 −2.15 
                 0.11 
                 −1.70 
                 0.17 
                 No 
                 No 
               
               
                 L612I 
                 −0.18 
                 0.13 
                 0.66 
                 0.11 
                 −0.24 
                 0.15 
                 Yes 
                 No 
               
               
                 L612K 
                 −1.41 
                 0.16 
                 −0.48 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612P 
                 −0.34 
                 0.06 
                 −0.33 
                 0.06 
                 −0.72 
                 0.11 
                 No 
                 No 
               
               
                 L612* 
                 −1.69 
                 0.15 
                 −0.55 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612T 
                 −0.27 
                 0.09 
                 −1.35 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L612V 
                 −1.05 
                 0.08 
                 −0.90 
                 0.08 
                 −1.51 
                 0.05 
                 No 
                 No 
               
               
                 K613R 
                 −0.22 
                 0.06 
                 −0.18 
                 0.06 
                 −0.40 
                 0.05 
                 No 
                 No 
               
               
                 K613N 
                 0.04 
                 0.10 
                 0.16 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613Q 
                 0.14 
                 0.04 
                 0.38 
                 0.04 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613E 
                 −0.75 
                 0.08 
                 0.06 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613G 
                 −1.17 
                 0.08 
                 −1.36 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613L 
                 0.12 
                 0.09 
                 0.49 
                 0.09 
                 −0.52 
                 0.26 
                 Yes 
                 No 
               
               
                 K613M 
                 −0.26 
                 0.11 
                 0.73 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613* 
                 −0.72 
                 0.11 
                 −0.72 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613T 
                 0.26 
                 0.05 
                 0.46 
                 0.05 
                 −0.65 
                 0.08 
                 Yes 
                 No 
               
               
                 K613W 
                 −1.27 
                 0.12 
                 −1.60 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K613V 
                 −0.89 
                 0.10 
                 −0.25 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614R 
                 0.28 
                 0.04 
                 0.07 
                 0.05 
                 0.16 
                 0.05 
                 Yes 
                 Yes 
               
               
                 A614I 
                 0.52 
                 0.11 
                 0.59 
                 0.11 
                 0.41 
                 0.22 
                 Yes 
                 Yes 
               
               
                 A614D 
                 −0.02 
                 0.08 
                 −0.34 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614C 
                 −0.54 
                 0.09 
                 −0.12 
                 0.08 
                 0.02 
                 0.22 
                 Yes 
                 No 
               
               
                 A614Q 
                 0.50 
                 0.10 
                 0.17 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614E 
                 −0.71 
                 0.08 
                 −0.80 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614G 
                 −0.16 
                 0.03 
                 0.09 
                 0.03 
                 −0.21 
                 0.08 
                 Yes 
                 No 
               
               
                 A614L 
                 0.09 
                 0.06 
                 −0.21 
                 0.06 
                 0.02 
                 0.12 
                 Yes 
                 No 
               
               
                 A614K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.28 
                 0.38 
                 Yes 
                 No 
               
               
                 A614M 
                 −0.39 
                 0.13 
                 1.39 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614F 
                 −0.66 
                 0.14 
                 −0.11 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A614P 
                 −0.22 
                 0.09 
                 −0.09 
                 0.09 
                 −0.68 
                 0.25 
                 No 
                 No 
               
               
                 A614S 
                 −0.46 
                 0.07 
                 0.19 
                 0.06 
                 −0.55 
                 0.15 
                 Yes 
                 No 
               
               
                 A614* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.35 
                 0.32 
                 Yes 
                 No 
               
               
                 A614T 
                 0.03 
                 0.06 
                 0.37 
                 0.06 
                 −0.49 
                 0.14 
                 Yes 
                 No 
               
               
                 A614W 
                 −0.74 
                 0.07 
                 −0.88 
                 0.08 
                 −0.97 
                 0.14 
                 No 
                 No 
               
               
                 A614V 
                 0.17 
                 0.04 
                 0.29 
                 0.04 
                 −0.03 
                 0.11 
                 Yes 
                 No 
               
               
                 V615A 
                 −0.05 
                 0.03 
                 0.09 
                 0.03 
                 −0.35 
                 0.04 
                 Yes 
                 No 
               
               
                 V615R 
                 −1.73 
                 0.05 
                 −1.23 
                 0.04 
                 −1.21 
                 0.07 
                 No 
                 No 
               
               
                 V615N 
                 −0.21 
                 0.08 
                 −1.01 
                 0.11 
                 −0.72 
                 0.15 
                 No 
                 No 
               
               
                 V615D 
                 −0.95 
                 0.07 
                 −0.97 
                 0.07 
                 −1.54 
                 0.13 
                 No 
                 No 
               
               
                 V615C 
                 −0.18 
                 0.06 
                 −0.18 
                 0.06 
                 −0.01 
                 0.19 
                 No 
                 No 
               
               
                 V615Q 
                 −1.87 
                 0.10 
                 −1.41 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V615E 
                 −0.82 
                 0.04 
                 −0.59 
                 0.04 
                 −1.03 
                 0.05 
                 No 
                 No 
               
               
                 V615G 
                 −0.57 
                 0.03 
                 −0.88 
                 0.03 
                 −1.19 
                 0.04 
                 No 
                 No 
               
               
                 V615I 
                 −0.51 
                 0.09 
                 −0.73 
                 0.10 
                 −0.67 
                 0.23 
                 No 
                 No 
               
               
                 V615L 
                 −0.07 
                 0.03 
                 0.05 
                 0.03 
                 −0.88 
                 0.05 
                 Yes 
                 No 
               
               
                 V615K 
                 −1.22 
                 0.08 
                 −1.81 
                 0.10 
                 −1.56 
                 0.07 
                 No 
                 No 
               
               
                 V615M 
                 −0.52 
                 0.06 
                 −0.54 
                 0.06 
                 −0.54 
                 0.12 
                 No 
                 No 
               
               
                 V615F 
                 −1.88 
                 0.14 
                 −1.30 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V615P 
                 −1.53 
                 0.10 
                 −1.82 
                 0.11 
                 −1.42 
                 0.06 
                 No 
                 No 
               
               
                 V615S 
                 0.17 
                 0.04 
                 −0.23 
                 0.04 
                 −0.63 
                 0.05 
                 Yes 
                 No 
               
               
                 V615* 
                 −1.04 
                 0.07 
                 −0.78 
                 0.07 
                 −1.35 
                 0.16 
                 No 
                 No 
               
               
                 V615T 
                 0.19 
                 0.05 
                 −0.12 
                 0.06 
                 −0.07 
                 0.17 
                 Yes 
                 No 
               
               
                 V615W 
                 −1.19 
                 0.06 
                 −1.55 
                 0.07 
                 −1.90 
                 0.05 
                 No 
                 No 
               
               
                 T616A 
                 0.32 
                 0.03 
                 0.24 
                 0.04 
                 0.09 
                 0.05 
                 Yes 
                 Yes 
               
               
                 T616R 
                 0.19 
                 0.03 
                 0.12 
                 0.03 
                 0.62 
                 0.04 
                 Yes 
                 Yes 
               
               
                 T616Q 
                 0.35 
                 0.07 
                 0.38 
                 0.07 
                 0.78 
                 0.20 
                 Yes 
                 Yes 
               
               
                 T616G 
                 0.22 
                 0.03 
                 0.01 
                 0.03 
                 0.16 
                 0.06 
                 Yes 
                 Yes 
               
               
                 T616Y 
                 0.54 
                 0.09 
                 0.64 
                 0.09 
                 0.05 
                 0.38 
                 Yes 
                 Yes 
               
               
                 T616N 
                 −0.11 
                 0.08 
                 0.20 
                 0.08 
                 0.16 
                 0.07 
                 Yes 
                 No 
               
               
                 T616D 
                 −0.66 
                 0.08 
                 0.14 
                 0.07 
                 −0.18 
                 0.26 
                 Yes 
                 No 
               
               
                 T616C 
                 0.54 
                 0.06 
                 0.27 
                 0.06 
                 −0.24 
                 0.11 
                 Yes 
                 No 
               
               
                 T616E 
                 −0.28 
                 0.06 
                 −0.38 
                 0.06 
                 −0.17 
                 0.07 
                 No 
                 No 
               
               
                 T616H 
                 0.62 
                 0.08 
                 −0.13 
                 0.10 
                 1.21 
                 0.25 
                 Yes 
                 No 
               
               
                 T616I 
                 −0.33 
                 0.08 
                 0.30 
                 0.07 
                 0.19 
                 0.18 
                 Yes 
                 No 
               
               
                 T616L 
                 −0.27 
                 0.05 
                 −0.43 
                 0.05 
                 −0.19 
                 0.13 
                 No 
                 No 
               
               
                 T616K 
                 −0.36 
                 0.08 
                 0.23 
                 0.07 
                 0.66 
                 0.09 
                 Yes 
                 No 
               
               
                 T616M 
                 −0.49 
                 0.08 
                 −0.40 
                 0.08 
                 −0.44 
                 0.25 
                 No 
                 No 
               
               
                 T616F 
                 −0.58 
                 0.11 
                 0.07 
                 0.09 
                 0.10 
                 0.36 
                 Yes 
                 No 
               
               
                 T616P 
                 −0.89 
                 0.07 
                 −0.68 
                 0.07 
                 −0.80 
                 0.06 
                 No 
                 No 
               
               
                 T616S 
                 −0.02 
                 0.04 
                 0.12 
                 0.04 
                 0.13 
                 0.07 
                 Yes 
                 No 
               
               
                 T616* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.14 
                 0.24 
                 Yes 
                 No 
               
               
                 T616W 
                 −0.28 
                 0.05 
                 0.25 
                 0.04 
                 −0.22 
                 0.19 
                 Yes 
                 No 
               
               
                 T616V 
                 −0.07 
                 0.04 
                 −0.09 
                 0.04 
                 0.21 
                 0.07 
                 Yes 
                 No 
               
               
                 A617G 
                 0.03 
                 0.03 
                 0.05 
                 0.03 
                 0.24 
                 0.06 
                 Yes 
                 Yes 
               
               
                 A617R 
                 −0.10 
                 0.04 
                 0.07 
                 0.04 
                 −0.32 
                 0.11 
                 Yes 
                 No 
               
               
                 A617N 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.12 
                 0.42 
                 Yes 
                 No 
               
               
                 A617D 
                 −0.76 
                 0.09 
                 −0.05 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A617C 
                 −0.73 
                 0.09 
                 0.26 
                 0.07 
                 0.13 
                 0.18 
                 Yes 
                 No 
               
               
                 A617Q 
                 0.25 
                 0.08 
                 0.07 
                 0.09 
                 −0.48 
                 0.30 
                 Yes 
                 No 
               
               
                 A617E 
                 −0.12 
                 0.06 
                 0.08 
                 0.06 
                 −0.40 
                 0.20 
                 Yes 
                 No 
               
               
                 A617H 
                 −0.11 
                 0.11 
                 −0.46 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A617I 
                 −0.26 
                 0.11 
                 0.09 
                 0.10 
                 −0.52 
                 0.38 
                 Yes 
                 No 
               
               
                 A617L 
                 −0.11 
                 0.05 
                 0.18 
                 0.05 
                 −0.18 
                 0.16 
                 Yes 
                 No 
               
               
                 A617K 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.08 
                 0.28 
                 Yes 
                 No 
               
               
                 A617M 
                 0.32 
                 0.07 
                 0.30 
                 0.07 
                 −0.34 
                 0.27 
                 Yes 
                 No 
               
               
                 A617F 
                 −0.17 
                 0.10 
                 −0.39 
                 0.11 
                 −0.42 
                 0.36 
                 No 
                 No 
               
               
                 A617P 
                 −0.48 
                 0.08 
                 −0.88 
                 0.09 
                 0.05 
                 0.18 
                 Yes 
                 No 
               
               
                 A617S 
                 −0.13 
                 0.05 
                 0.25 
                 0.05 
                 −0.58 
                 0.06 
                 Yes 
                 No 
               
               
                 A617* 
                 −0.96 
                 0.11 
                 −1.57 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A617T 
                 −0.23 
                 0.05 
                 0.26 
                 0.05 
                 −0.30 
                 0.10 
                 Yes 
                 No 
               
               
                 A617W 
                 0.17 
                 0.05 
                 −0.93 
                 0.07 
                 −0.69 
                 0.15 
                 Yes 
                 No 
               
               
                 A617V 
                 −0.03 
                 0.04 
                 −0.09 
                 0.04 
                 −0.42 
                 0.12 
                 No 
                 No 
               
               
                 H618A 
                 −0.73 
                 0.14 
                 −0.80 
                 0.15 
                 0.36 
                 0.36 
                 Yes 
                 No 
               
               
                 H618R 
                 −0.08 
                 0.05 
                 0.24 
                 0.05 
                 −0.46 
                 0.06 
                 Yes 
                 No 
               
               
                 H618N 
                 −0.37 
                 0.17 
                 −0.24 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H618D 
                 0.48 
                 0.13 
                 0.89 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H618Q 
                 −0.62 
                 0.14 
                 0.01 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H618G 
                 −0.56 
                 0.07 
                 −0.91 
                 0.09 
                 −0.91 
                 0.19 
                 No 
                 No 
               
               
                 H618L 
                 0.02 
                 0.06 
                 0.10 
                 0.06 
                 −0.47 
                 0.07 
                 Yes 
                 No 
               
               
                 H618P 
                 0.32 
                 0.08 
                 0.47 
                 0.08 
                 −0.51 
                 0.08 
                 Yes 
                 No 
               
               
                 H618S 
                 −0.50 
                 0.14 
                 −0.26 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H618W 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.44 
                 0.31 
                 Yes 
                 No 
               
               
                 H618Y 
                 0.23 
                 0.10 
                 −0.28 
                 0.11 
                 −0.26 
                 0.19 
                 Yes 
                 No 
               
               
                 F619M 
                 0.12 
                 0.07 
                 0.55 
                 0.07 
                 0.22 
                 0.25 
                 Yes 
                 Yes 
               
               
                 F619A 
                 −0.57 
                 0.05 
                 −1.25 
                 0.06 
                 −0.78 
                 0.05 
                 No 
                 No 
               
               
                 F619R 
                 −1.24 
                 0.05 
                 −1.94 
                 0.07 
                 −0.66 
                 0.07 
                 No 
                 No 
               
               
                 F619N 
                 −0.61 
                 0.13 
                 −0.15 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F619D 
                 −1.39 
                 0.12 
                 −0.62 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F619C 
                 0.07 
                 0.03 
                 0.08 
                 0.03 
                 −0.37 
                 0.04 
                 Yes 
                 No 
               
               
                 F619Q 
                 −1.13 
                 0.12 
                 −1.57 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F619E 
                 −1.58 
                 0.08 
                 −2.40 
                 0.12 
                 −1.54 
                 0.08 
                 No 
                 No 
               
               
                 F619G 
                 −1.29 
                 0.03 
                 −1.03 
                 0.03 
                 −1.57 
                 0.05 
                 No 
                 No 
               
               
                 F619H 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.31 
                 0.34 
                 Yes 
                 No 
               
               
                 F619I 
                 −0.69 
                 0.12 
                 −0.28 
                 0.11 
                 −0.42 
                 0.22 
                 No 
                 No 
               
               
                 F619L 
                 0.17 
                 0.03 
                 0.12 
                 0.03 
                 −0.48 
                 0.05 
                 Yes 
                 No 
               
               
                 F619P 
                 −1.00 
                 0.09 
                 −1.22 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F619S 
                 −0.26 
                 0.04 
                 −0.95 
                 0.06 
                 −0.56 
                 0.06 
                 No 
                 No 
               
               
                 F619* 
                 −1.91 
                 0.14 
                 −0.92 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F619T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.08 
                 0.24 
                 Yes 
                 No 
               
               
                 F619W 
                 −0.08 
                 0.04 
                 −0.81 
                 0.05 
                 0.00 
                 0.07 
                 Yes 
                 No 
               
               
                 F619Y 
                 0.06 
                 0.08 
                 −0.79 
                 0.11 
                 0.28 
                 0.11 
                 Yes 
                 No 
               
               
                 F619V 
                 −0.51 
                 0.04 
                 −0.49 
                 0.04 
                 −0.64 
                 0.04 
                 No 
                 No 
               
               
                 Q620A 
                 0.22 
                 0.04 
                 0.00 
                 0.05 
                 0.18 
                 0.09 
                 Yes 
                 Yes 
               
               
                 Q620R 
                 0.25 
                 0.03 
                 0.18 
                 0.03 
                 0.17 
                 0.04 
                 Yes 
                 Yes 
               
               
                 Q620N 
                 0.26 
                 0.14 
                 0.28 
                 0.14 
                 0.36 
                 0.21 
                 Yes 
                 Yes 
               
               
                 Q620L 
                 0.14 
                 0.04 
                 0.45 
                 0.04 
                 0.40 
                 0.16 
                 Yes 
                 Yes 
               
               
                 Q620K 
                 0.10 
                 0.07 
                 0.24 
                 0.07 
                 0.04 
                 0.10 
                 Yes 
                 Yes 
               
               
                 Q620D 
                 −0.16 
                 0.07 
                 −0.25 
                 0.08 
                 0.24 
                 0.23 
                 Yes 
                 No 
               
               
                 Q620C 
                 −0.22 
                 0.07 
                 −0.95 
                 0.10 
                 0.03 
                 0.23 
                 Yes 
                 No 
               
               
                 Q620E 
                 0.21 
                 0.05 
                 0.13 
                 0.05 
                 −0.09 
                 0.10 
                 Yes 
                 No 
               
               
                 Q620G 
                 −0.14 
                 0.02 
                 0.02 
                 0.02 
                 0.19 
                 0.04 
                 Yes 
                 No 
               
               
                 Q620H 
                 −0.08 
                 0.08 
                 0.16 
                 0.08 
                 −0.05 
                 0.20 
                 Yes 
                 No 
               
               
                 Q620I 
                 0.27 
                 0.11 
                 −0.38 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q620M 
                 0.70 
                 0.07 
                 −0.03 
                 0.08 
                 0.20 
                 0.26 
                 Yes 
                 No 
               
               
                 Q620F 
                 0.37 
                 0.11 
                 1.00 
                 0.10 
                 −0.47 
                 0.44 
                 Yes 
                 No 
               
               
                 Q620P 
                 −0.04 
                 0.06 
                 0.12 
                 0.06 
                 −0.26 
                 0.10 
                 Yes 
                 No 
               
               
                 Q620S 
                 0.17 
                 0.05 
                 −0.15 
                 0.06 
                 0.16 
                 0.17 
                 Yes 
                 No 
               
               
                 Q620* 
                 −0.82 
                 0.08 
                 −0.58 
                 0.07 
                 −0.64 
                 0.15 
                 No 
                 No 
               
               
                 Q620T 
                 −0.20 
                 0.09 
                 0.41 
                 0.08 
                 0.17 
                 0.12 
                 Yes 
                 No 
               
               
                 Q620W 
                 −0.12 
                 0.04 
                 0.09 
                 0.04 
                 0.08 
                 0.11 
                 Yes 
                 No 
               
               
                 Q620Y 
                 −0.74 
                 0.14 
                 0.21 
                 0.11 
                 −0.19 
                 0.38 
                 Yes 
                 No 
               
               
                 Q620V 
                 0.29 
                 0.03 
                 −0.11 
                 0.04 
                 0.26 
                 0.07 
                 Yes 
                 No 
               
               
                 T621A 
                 0.18 
                 0.04 
                 0.13 
                 0.04 
                 0.17 
                 0.10 
                 Yes 
                 Yes 
               
               
                 T621R 
                 −0.04 
                 0.04 
                 −0.45 
                 0.05 
                 −0.06 
                 0.15 
                 No 
                 No 
               
               
                 T621N 
                 −0.39 
                 0.12 
                 −0.09 
                 0.11 
                 0.02 
                 0.21 
                 Yes 
                 No 
               
               
                 T621D 
                 0.12 
                 0.12 
                 0.26 
                 0.12 
                 −0.11 
                 0.44 
                 Yes 
                 No 
               
               
                 T621C 
                 0.07 
                 0.09 
                 −0.29 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T621Q 
                 −0.90 
                 0.12 
                 0.06 
                 0.10 
                 0.44 
                 0.38 
                 Yes 
                 No 
               
               
                 T621E 
                 −0.29 
                 0.07 
                 0.13 
                 0.06 
                 −0.05 
                 0.24 
                 Yes 
                 No 
               
               
                 T621G 
                 −0.02 
                 0.03 
                 −0.21 
                 0.04 
                 0.48 
                 0.04 
                 Yes 
                 No 
               
               
                 T621H 
                 0.33 
                 0.15 
                 0.72 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T621I 
                 0.36 
                 0.08 
                 −0.09 
                 0.10 
                 0.21 
                 0.20 
                 Yes 
                 No 
               
               
                 T621L 
                 0.16 
                 0.06 
                 −0.40 
                 0.07 
                 −0.30 
                 0.10 
                 Yes 
                 No 
               
               
                 T621K 
                 −0.02 
                 0.09 
                 −0.09 
                 0.09 
                 −0.08 
                 0.37 
                 No 
                 No 
               
               
                 T621M 
                 0.21 
                 0.07 
                 −0.15 
                 0.08 
                 1.17 
                 0.09 
                 Yes 
                 No 
               
               
                 T621F 
                 −0.61 
                 0.16 
                 −0.16 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T621P 
                 0.04 
                 0.04 
                 0.18 
                 0.04 
                 −0.38 
                 0.06 
                 Yes 
                 No 
               
               
                 T621S 
                 −0.06 
                 0.06 
                 −0.08 
                 0.06 
                 0.28 
                 0.09 
                 Yes 
                 No 
               
               
                 T621W 
                 −0.21 
                 0.06 
                 0.08 
                 0.06 
                 0.12 
                 0.17 
                 Yes 
                 No 
               
               
                 T621Y 
                 −0.23 
                 0.16 
                 0.36 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T621V 
                 −0.28 
                 0.05 
                 0.32 
                 0.05 
                 0.32 
                 0.19 
                 Yes 
                 No 
               
               
                 H622G 
                 0.05 
                 0.03 
                 0.18 
                 0.03 
                 0.07 
                 0.06 
                 Yes 
                 Yes 
               
               
                 H622S 
                 0.16 
                 0.06 
                 0.59 
                 0.06 
                 0.08 
                 0.10 
                 Yes 
                 Yes 
               
               
                 H622T 
                 0.01 
                 0.09 
                 0.84 
                 0.08 
                 0.31 
                 0.34 
                 Yes 
                 Yes 
               
               
                 H622V 
                 0.18 
                 0.05 
                 0.15 
                 0.05 
                 0.31 
                 0.12 
                 Yes 
                 Yes 
               
               
                 H622A 
                 −0.17 
                 0.06 
                 0.16 
                 0.06 
                 0.41 
                 0.08 
                 Yes 
                 No 
               
               
                 H622R 
                 −0.19 
                 0.04 
                 0.12 
                 0.04 
                 0.05 
                 0.04 
                 Yes 
                 No 
               
               
                 H622N 
                 −0.05 
                 0.07 
                 0.30 
                 0.07 
                 −0.11 
                 0.12 
                 Yes 
                 No 
               
               
                 H622D 
                 −0.84 
                 0.11 
                 0.63 
                 0.07 
                 0.48 
                 0.10 
                 Yes 
                 No 
               
               
                 H622C 
                 −0.50 
                 0.09 
                 −0.10 
                 0.08 
                 0.11 
                 0.11 
                 Yes 
                 No 
               
               
                 H622Q 
                 −0.06 
                 0.08 
                 0.29 
                 0.07 
                 −0.14 
                 0.05 
                 Yes 
                 No 
               
               
                 H622E 
                 −0.11 
                 0.07 
                 0.15 
                 0.06 
                 0.23 
                 0.10 
                 Yes 
                 No 
               
               
                 H622I 
                 −0.05 
                 0.14 
                 0.45 
                 0.13 
                 0.36 
                 0.49 
                 Yes 
                 No 
               
               
                 H622L 
                 −0.49 
                 0.06 
                 0.06 
                 0.05 
                 −0.14 
                 0.11 
                 Yes 
                 No 
               
               
                 H622K 
                 0.29 
                 0.10 
                 1.39 
                 0.08 
                 0.00 
                 0.28 
                 Yes 
                 No 
               
               
                 H622M 
                 −0.07 
                 0.11 
                 −0.07 
                 0.11 
                 0.05 
                 0.34 
                 Yes 
                 No 
               
               
                 H622F 
                 0.14 
                 0.11 
                 −0.61 
                 0.14 
                 0.07 
                 0.13 
                 Yes 
                 No 
               
               
                 H622P 
                 0.14 
                 0.03 
                 0.25 
                 0.03 
                 −0.44 
                 0.04 
                 Yes 
                 No 
               
               
                 H622* 
                 −1.50 
                 0.13 
                 −1.18 
                 0.12 
                 −0.74 
                 0.16 
                 No 
                 No 
               
               
                 H622W 
                 0.08 
                 0.05 
                 0.21 
                 0.05 
                 −0.08 
                 0.19 
                 Yes 
                 No 
               
               
                 H622Y 
                 0.07 
                 0.09 
                 0.14 
                 0.09 
                 −0.08 
                 0.18 
                 Yes 
                 No 
               
               
                 T623E 
                 0.32 
                 0.05 
                 0.23 
                 0.05 
                 0.02 
                 0.05 
                 Yes 
                 Yes 
               
               
                 T623H 
                 0.60 
                 0.10 
                 0.01 
                 0.11 
                 0.58 
                 0.55 
                 Yes 
                 Yes 
               
               
                 T623L 
                 0.33 
                 0.05 
                 0.18 
                 0.05 
                 0.17 
                 0.16 
                 Yes 
                 Yes 
               
               
                 T623M 
                 0.21 
                 0.07 
                 0.28 
                 0.07 
                 0.59 
                 0.22 
                 Yes 
                 Yes 
               
               
                 T623F 
                 0.80 
                 0.10 
                 0.61 
                 0.10 
                 0.47 
                 0.32 
                 Yes 
                 Yes 
               
               
                 T623A 
                 −0.14 
                 0.04 
                 0.35 
                 0.03 
                 −0.04 
                 0.07 
                 Yes 
                 No 
               
               
                 T623R 
                 −0.16 
                 0.03 
                 −0.40 
                 0.04 
                 0.15 
                 0.09 
                 Yes 
                 No 
               
               
                 T623N 
                 0.02 
                 0.09 
                 0.19 
                 0.09 
                 −0.28 
                 0.16 
                 Yes 
                 No 
               
               
                 T623D 
                 −0.69 
                 0.09 
                 0.41 
                 0.07 
                 −0.34 
                 0.14 
                 Yes 
                 No 
               
               
                 T623C 
                 −0.39 
                 0.08 
                 0.01 
                 0.08 
                 0.40 
                 0.28 
                 Yes 
                 No 
               
               
                 T623Q 
                 0.23 
                 0.07 
                 0.38 
                 0.07 
                 −0.01 
                 0.32 
                 Yes 
                 No 
               
               
                 T623G 
                 −0.40 
                 0.03 
                 −0.09 
                 0.03 
                 −0.05 
                 0.03 
                 No 
                 No 
               
               
                 T623I 
                 −0.59 
                 0.10 
                 0.11 
                 0.08 
                 −0.13 
                 0.13 
                 Yes 
                 No 
               
               
                 T623K 
                 1.10 
                 0.07 
                 −0.02 
                 0.08 
                 0.53 
                 0.17 
                 Yes 
                 No 
               
               
                 T623P 
                 −0.16 
                 0.06 
                 −0.29 
                 0.07 
                 −0.11 
                 0.17 
                 No 
                 No 
               
               
                 T623S 
                 0.67 
                 0.04 
                 0.21 
                 0.04 
                 −0.06 
                 0.07 
                 Yes 
                 No 
               
               
                 T623W 
                 −0.01 
                 0.05 
                 −0.29 
                 0.06 
                 −0.27 
                 0.10 
                 No 
                 No 
               
               
                 T623Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.11 
                 0.29 
                 Yes 
                 No 
               
               
                 T623V 
                 −0.26 
                 0.04 
                 −0.20 
                 0.04 
                 0.41 
                 0.05 
                 Yes 
                 No 
               
               
                 T624P 
                 0.92 
                 0.02 
                 0.92 
                 0.02 
                 0.04 
                 0.03 
                 Yes 
                 Yes 
               
               
                 T624A 
                 0.65 
                 0.02 
                 0.76 
                 0.02 
                 −0.07 
                 0.03 
                 Yes 
                 No 
               
               
                 T624R 
                 0.41 
                 0.07 
                 0.34 
                 0.07 
                 −0.55 
                 0.23 
                 Yes 
                 No 
               
               
                 T624N 
                 0.15 
                 0.10 
                 0.20 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T624C 
                 −0.20 
                 0.15 
                 0.21 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T624E 
                 0.38 
                 0.09 
                 −0.63 
                 0.12 
                 −0.11 
                 0.55 
                 Yes 
                 No 
               
               
                 T624G 
                 −0.21 
                 0.06 
                 0.12 
                 0.06 
                 0.15 
                 0.21 
                 Yes 
                 No 
               
               
                 T624I 
                 0.58 
                 0.11 
                 0.35 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T624L 
                 0.41 
                 0.09 
                 −0.84 
                 0.13 
                 0.96 
                 0.48 
                 Yes 
                 No 
               
               
                 T624S 
                 1.15 
                 0.04 
                 1.20 
                 0.04 
                 −0.13 
                 0.04 
                 Yes 
                 No 
               
               
                 T624W 
                 0.56 
                 0.10 
                 −0.20 
                 0.12 
                 0.10 
                 0.16 
                 Yes 
                 No 
               
               
                 T624V 
                 −0.12 
                 0.08 
                 −0.52 
                 0.10 
                 0.18 
                 0.23 
                 Yes 
                 No 
               
               
                 P625A 
                 −0.27 
                 0.11 
                 0.30 
                 0.10 
                 0.31 
                 0.10 
                 Yes 
                 No 
               
               
                 P625R 
                 0.06 
                 0.07 
                 −1.01 
                 0.10 
                 −0.04 
                 0.22 
                 Yes 
                 No 
               
               
                 P625C 
                 0.56 
                 0.14 
                 −0.17 
                 0.16 
                 −0.02 
                 0.82 
                 Yes 
                 No 
               
               
                 P625E 
                 −0.24 
                 0.13 
                 −0.22 
                 0.13 
                 −0.41 
                 0.64 
                 No 
                 No 
               
               
                 P625G 
                 −0.41 
                 0.08 
                 0.40 
                 0.06 
                 0.04 
                 0.24 
                 Yes 
                 No 
               
               
                 P625H 
                 −0.25 
                 0.15 
                 −0.02 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P625L 
                 −0.48 
                 0.09 
                 −0.82 
                 0.11 
                 −0.56 
                 0.17 
                 No 
                 No 
               
               
                 P625S 
                 −0.38 
                 0.08 
                 −0.55 
                 0.09 
                 0.03 
                 0.20 
                 Yes 
                 No 
               
               
                 P625T 
                 0.30 
                 0.08 
                 0.23 
                 0.08 
                 −0.06 
                 0.10 
                 Yes 
                 No 
               
               
                 P625W 
                 −0.60 
                 0.13 
                 −0.64 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P625V 
                 −0.17 
                 0.09 
                 −0.63 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I626A 
                 0.16 
                 0.12 
                 0.80 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I626R 
                 −0.89 
                 0.12 
                 0.14 
                 0.09 
                 −0.09 
                 0.31 
                 Yes 
                 No 
               
               
                 I626N 
                 0.42 
                 0.04 
                 0.61 
                 0.04 
                 −0.37 
                 0.06 
                 Yes 
                 No 
               
               
                 I626E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.15 
                 0.55 
                 Yes 
                 No 
               
               
                 I626G 
                 −1.04 
                 0.10 
                 −1.35 
                 0.12 
                 −0.48 
                 0.27 
                 No 
                 No 
               
               
                 I626L 
                 0.61 
                 0.11 
                 −0.85 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I626S 
                 0.36 
                 0.04 
                 0.60 
                 0.04 
                 −0.65 
                 0.07 
                 Yes 
                 No 
               
               
                 I626T 
                 0.17 
                 0.02 
                 0.34 
                 0.02 
                 −0.37 
                 0.03 
                 Yes 
                 No 
               
               
                 I626W 
                 −0.74 
                 0.16 
                 0.22 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I626V 
                 −0.51 
                 0.10 
                 0.05 
                 0.09 
                 0.10 
                 0.18 
                 Yes 
                 No 
               
               
                 L627C 
                 0.14 
                 0.13 
                 0.84 
                 0.11 
                 0.57 
                 0.48 
                 Yes 
                 Yes 
               
               
                 L627A 
                 0.00 
                 0.08 
                 0.24 
                 0.08 
                 1.31 
                 0.29 
                 Yes 
                 No 
               
               
                 L627R 
                 0.29 
                 0.04 
                 0.03 
                 0.04 
                 −0.10 
                 0.05 
                 Yes 
                 No 
               
               
                 L627N 
                 0.71 
                 0.15 
                 1.09 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L627D 
                 0.32 
                 0.10 
                 −1.12 
                 0.16 
                 1.13 
                 0.55 
                 Yes 
                 No 
               
               
                 L627Q 
                 0.23 
                 0.07 
                 0.39 
                 0.07 
                 −0.27 
                 0.11 
                 Yes 
                 No 
               
               
                 L627E 
                 0.29 
                 0.07 
                 −0.06 
                 0.08 
                 0.17 
                 0.11 
                 Yes 
                 No 
               
               
                 L627G 
                 −0.04 
                 0.04 
                 −0.01 
                 0.04 
                 0.23 
                 0.10 
                 Yes 
                 No 
               
               
                 L627K 
                 0.57 
                 0.11 
                 0.27 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L627M 
                 −0.57 
                 0.12 
                 0.33 
                 0.10 
                 −0.09 
                 0.22 
                 Yes 
                 No 
               
               
                 L627P 
                 0.10 
                 0.05 
                 0.31 
                 0.05 
                 −0.25 
                 0.08 
                 Yes 
                 No 
               
               
                 L627S 
                 0.34 
                 0.08 
                 0.18 
                 0.08 
                 −0.29 
                 0.27 
                 Yes 
                 No 
               
               
                 L627* 
                 0.52 
                 0.10 
                 −0.87 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L627T 
                 0.60 
                 0.09 
                 −0.76 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L627W 
                 −0.71 
                 0.09 
                 0.85 
                 0.07 
                 0.27 
                 0.32 
                 Yes 
                 No 
               
               
                 L627V 
                 −0.89 
                 0.08 
                 0.48 
                 0.06 
                 −0.23 
                 0.19 
                 Yes 
                 No 
               
               
                 L628C 
                 0.31 
                 0.09 
                 0.10 
                 0.10 
                 0.29 
                 0.31 
                 Yes 
                 Yes 
               
               
                 L628W 
                 0.25 
                 0.06 
                 0.01 
                 0.07 
                 0.67 
                 0.15 
                 Yes 
                 Yes 
               
               
                 L628A 
                 −0.22 
                 0.06 
                 −0.58 
                 0.07 
                 −0.36 
                 0.11 
                 No 
                 No 
               
               
                 L628R 
                 −0.13 
                 0.04 
                 −0.50 
                 0.05 
                 0.53 
                 0.06 
                 Yes 
                 No 
               
               
                 L628Q 
                 −0.10 
                 0.10 
                 −0.04 
                 0.10 
                 −0.36 
                 0.23 
                 No 
                 No 
               
               
                 L628E 
                 −0.73 
                 0.10 
                 −1.59 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L628G 
                 −0.65 
                 0.04 
                 −1.57 
                 0.06 
                 −0.96 
                 0.14 
                 No 
                 No 
               
               
                 L628I 
                 −0.47 
                 0.17 
                 −0.57 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L628K 
                 0.75 
                 0.11 
                 −0.44 
                 0.15 
                 −0.21 
                 0.31 
                 Yes 
                 No 
               
               
                 L628M 
                 −0.49 
                 0.09 
                 −0.37 
                 0.09 
                 −0.21 
                 0.12 
                 No 
                 No 
               
               
                 L628P 
                 −0.27 
                 0.08 
                 −0.45 
                 0.08 
                 −0.39 
                 0.14 
                 No 
                 No 
               
               
                 L628S 
                 −0.78 
                 0.08 
                 −1.36 
                 0.10 
                 −0.83 
                 0.21 
                 No 
                 No 
               
               
                 L628T 
                 −0.16 
                 0.10 
                 −0.52 
                 0.12 
                 −0.60 
                 0.27 
                 No 
                 No 
               
               
                 L628V 
                 −0.13 
                 0.05 
                 0.34 
                 0.05 
                 −0.31 
                 0.09 
                 Yes 
                 No 
               
               
                 S629A 
                 −0.99 
                 0.12 
                 0.49 
                 0.08 
                 −0.09 
                 0.29 
                 Yes 
                 No 
               
               
                 S629R 
                 0.10 
                 0.02 
                 0.29 
                 0.02 
                 −0.37 
                 0.03 
                 Yes 
                 No 
               
               
                 S629N 
                 0.40 
                 0.05 
                 0.36 
                 0.05 
                 −0.32 
                 0.08 
                 Yes 
                 No 
               
               
                 S629D 
                 −0.54 
                 0.18 
                 −0.23 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S629C 
                 0.30 
                 0.10 
                 0.10 
                 0.11 
                 −0.08 
                 0.21 
                 Yes 
                 No 
               
               
                 S629Q 
                 0.76 
                 0.17 
                 0.40 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S629E 
                 0.84 
                 0.10 
                 0.61 
                 0.11 
                 −0.08 
                 0.48 
                 Yes 
                 No 
               
               
                 S629G 
                 −0.30 
                 0.05 
                 0.40 
                 0.05 
                 0.09 
                 0.08 
                 Yes 
                 No 
               
               
                 S629I 
                 0.05 
                 0.14 
                 0.42 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S629L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.03 
                 0.36 
                 Yes 
                 No 
               
               
                 S629K 
                 0.37 
                 0.13 
                 0.80 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S629P 
                 −0.03 
                 0.15 
                 −0.34 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S629T 
                 −0.60 
                 0.13 
                 0.01 
                 0.11 
                 0.22 
                 0.32 
                 Yes 
                 No 
               
               
                 S629W 
                 −0.03 
                 0.11 
                 −0.66 
                 0.13 
                 0.42 
                 0.54 
                 Yes 
                 No 
               
               
                 S629V 
                 −0.87 
                 0.11 
                 −0.82 
                 0.11 
                 0.05 
                 0.14 
                 Yes 
                 No 
               
               
                 N630R 
                 0.53 
                 0.05 
                 0.06 
                 0.06 
                 0.94 
                 0.08 
                 Yes 
                 Yes 
               
               
                 N630A 
                 −0.53 
                 0.09 
                 0.62 
                 0.07 
                 −0.06 
                 0.23 
                 Yes 
                 No 
               
               
                 N630D 
                 −0.33 
                 0.09 
                 0.49 
                 0.07 
                 −0.22 
                 0.14 
                 Yes 
                 No 
               
               
                 N630C 
                 0.42 
                 0.10 
                 −0.12 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N630E 
                 −0.67 
                 0.09 
                 0.69 
                 0.07 
                 −0.30 
                 0.26 
                 Yes 
                 No 
               
               
                 N630G 
                 0.32 
                 0.04 
                 −0.11 
                 0.04 
                 0.22 
                 0.10 
                 Yes 
                 No 
               
               
                 N630H 
                 0.06 
                 0.10 
                 0.51 
                 0.09 
                 −0.29 
                 0.13 
                 Yes 
                 No 
               
               
                 N630I 
                 −0.45 
                 0.12 
                 0.44 
                 0.10 
                 −0.27 
                 0.18 
                 Yes 
                 No 
               
               
                 N630L 
                 −0.24 
                 0.09 
                 0.55 
                 0.08 
                 −0.78 
                 0.15 
                 Yes 
                 No 
               
               
                 N630K 
                 0.37 
                 0.10 
                 0.93 
                 0.09 
                 −0.25 
                 0.18 
                 Yes 
                 No 
               
               
                 N630F 
                 −0.58 
                 0.18 
                 −0.11 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N630S 
                 0.34 
                 0.06 
                 −0.21 
                 0.07 
                 0.16 
                 0.13 
                 Yes 
                 No 
               
               
                 N630T 
                 0.16 
                 0.03 
                 0.38 
                 0.02 
                 −0.53 
                 0.04 
                 Yes 
                 No 
               
               
                 N630W 
                 −0.11 
                 0.09 
                 −1.04 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N630Y 
                 −0.24 
                 0.12 
                 0.59 
                 0.10 
                 0.14 
                 0.19 
                 Yes 
                 No 
               
               
                 N630V 
                 −0.20 
                 0.06 
                 −0.90 
                 0.08 
                 −0.26 
                 0.18 
                 No 
                 No 
               
               
                 N631A 
                 −0.03 
                 0.07 
                 0.06 
                 0.07 
                 −0.70 
                 0.25 
                 Yes 
                 No 
               
               
                 N631R 
                 −0.11 
                 0.06 
                 0.27 
                 0.05 
                 1.20 
                 0.07 
                 Yes 
                 No 
               
               
                 N631D 
                 −0.56 
                 0.10 
                 −0.38 
                 0.09 
                 −0.77 
                 0.13 
                 No 
                 No 
               
               
                 N631C 
                 −0.71 
                 0.15 
                 −0.64 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N631E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.95 
                 0.23 
                 Yes 
                 No 
               
               
                 N631G 
                 −0.67 
                 0.05 
                 −0.39 
                 0.05 
                 −1.02 
                 0.07 
                 No 
                 No 
               
               
                 N631I 
                 0.31 
                 0.10 
                 −0.62 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N631L 
                 −1.12 
                 0.10 
                 −0.57 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N631K 
                 −0.05 
                 0.08 
                 −0.20 
                 0.09 
                 0.70 
                 0.11 
                 Yes 
                 No 
               
               
                 N631M 
                 −0.10 
                 0.10 
                 0.36 
                 0.09 
                 −0.27 
                 0.30 
                 Yes 
                 No 
               
               
                 N631P 
                 0.06 
                 0.12 
                 0.30 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N631S 
                 0.15 
                 0.06 
                 0.06 
                 0.06 
                 −0.36 
                 0.13 
                 Yes 
                 No 
               
               
                 N631T 
                 0.07 
                 0.04 
                 0.24 
                 0.04 
                 −0.37 
                 0.05 
                 Yes 
                 No 
               
               
                 N631Y 
                 −0.48 
                 0.12 
                 −0.03 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N631V 
                 −0.66 
                 0.07 
                 −1.17 
                 0.08 
                 −0.78 
                 0.23 
                 No 
                 No 
               
               
                 F632A 
                 −0.79 
                 0.07 
                 −1.34 
                 0.09 
                 −1.29 
                 0.12 
                 No 
                 No 
               
               
                 F632R 
                 −0.76 
                 0.05 
                 −0.40 
                 0.05 
                 −0.13 
                 0.05 
                 No 
                 No 
               
               
                 F632D 
                 −1.62 
                 0.15 
                 −1.61 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632C 
                 0.66 
                 0.02 
                 0.78 
                 0.02 
                 −0.06 
                 0.02 
                 Yes 
                 No 
               
               
                 F632Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.18 
                 0.55 
                 Yes 
                 No 
               
               
                 F632E 
                 −1.35 
                 0.10 
                 −0.87 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632G 
                 −0.01 
                 0.03 
                 0.12 
                 0.03 
                 −0.03 
                 0.02 
                 Yes 
                 No 
               
               
                 F632H 
                 −0.31 
                 0.16 
                 0.08 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632I 
                 −0.33 
                 0.10 
                 −0.01 
                 0.10 
                 −0.87 
                 0.13 
                 No 
                 No 
               
               
                 F632L 
                 −0.28 
                 0.05 
                 0.22 
                 0.05 
                 −0.26 
                 0.07 
                 Yes 
                 No 
               
               
                 F632K 
                 −0.49 
                 0.13 
                 0.74 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632M 
                 0.00 
                 0.10 
                 0.16 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632S 
                 −0.75 
                 0.06 
                 −0.56 
                 0.06 
                 −0.83 
                 0.06 
                 No 
                 No 
               
               
                 F632* 
                 −0.69 
                 0.12 
                 −0.55 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632T 
                 −0.09 
                 0.09 
                 −0.80 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F632W 
                 0.17 
                 0.06 
                 −0.14 
                 0.06 
                 −0.44 
                 0.19 
                 Yes 
                 No 
               
               
                 F632Y 
                 −0.15 
                 0.08 
                 0.38 
                 0.07 
                 −0.07 
                 0.10 
                 Yes 
                 No 
               
               
                 F632V 
                 0.38 
                 0.02 
                 0.41 
                 0.02 
                 −0.07 
                 0.02 
                 Yes 
                 No 
               
               
                 I633N 
                 0.16 
                 0.06 
                 0.65 
                 0.06 
                 0.15 
                 0.10 
                 Yes 
                 Yes 
               
               
                 I633M 
                 0.17 
                 0.07 
                 0.28 
                 0.07 
                 0.10 
                 0.19 
                 Yes 
                 Yes 
               
               
                 I633S 
                 0.02 
                 0.04 
                 0.35 
                 0.04 
                 0.22 
                 0.08 
                 Yes 
                 Yes 
               
               
                 I633A 
                 0.15 
                 0.05 
                 −0.24 
                 0.06 
                 0.42 
                 0.13 
                 Yes 
                 No 
               
               
                 I633R 
                 −0.42 
                 0.04 
                 0.41 
                 0.04 
                 0.22 
                 0.06 
                 Yes 
                 No 
               
               
                 I633D 
                 −0.62 
                 0.09 
                 −0.01 
                 0.08 
                 −0.12 
                 0.10 
                 No 
                 No 
               
               
                 I633C 
                 0.15 
                 0.07 
                 −0.34 
                 0.08 
                 −0.04 
                 0.14 
                 Yes 
                 No 
               
               
                 I633Q 
                 −0.26 
                 0.10 
                 1.05 
                 0.08 
                 −0.37 
                 0.22 
                 Yes 
                 No 
               
               
                 I633E 
                 −0.98 
                 0.07 
                 −0.34 
                 0.06 
                 0.30 
                 0.11 
                 Yes 
                 No 
               
               
                 I633G 
                 −0.09 
                 0.03 
                 0.10 
                 0.03 
                 0.05 
                 0.06 
                 Yes 
                 No 
               
               
                 I633H 
                 −0.71 
                 0.14 
                 −0.16 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I633L 
                 −0.10 
                 0.05 
                 0.00 
                 0.05 
                 0.25 
                 0.06 
                 Yes 
                 No 
               
               
                 I633K 
                 −0.29 
                 0.09 
                 0.17 
                 0.08 
                 0.63 
                 0.29 
                 Yes 
                 No 
               
               
                 I633F 
                 −0.11 
                 0.09 
                 0.24 
                 0.09 
                 0.51 
                 0.22 
                 Yes 
                 No 
               
               
                 I633P 
                 0.23 
                 0.08 
                 −0.90 
                 0.12 
                 0.19 
                 0.31 
                 Yes 
                 No 
               
               
                 I633* 
                 −1.45 
                 0.12 
                 −1.53 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I633T 
                 0.13 
                 0.04 
                 0.40 
                 0.04 
                 −0.17 
                 0.06 
                 Yes 
                 No 
               
               
                 I633W 
                 −0.35 
                 0.05 
                 0.14 
                 0.05 
                 −0.07 
                 0.09 
                 Yes 
                 No 
               
               
                 I633Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.09 
                 0.34 
                 Yes 
                 No 
               
               
                 I633V 
                 0.09 
                 0.04 
                 −0.06 
                 0.04 
                 0.39 
                 0.06 
                 Yes 
                 No 
               
               
                 E634N 
                 0.52 
                 0.12 
                 0.46 
                 0.12 
                 0.00 
                 0.36 
                 Yes 
                 Yes 
               
               
                 E634A 
                 0.20 
                 0.02 
                 0.38 
                 0.02 
                 −0.36 
                 0.03 
                 Yes 
                 No 
               
               
                 E634R 
                 −0.06 
                 0.04 
                 0.30 
                 0.04 
                 0.33 
                 0.08 
                 Yes 
                 No 
               
               
                 E634D 
                 −0.10 
                 0.06 
                 0.30 
                 0.06 
                 0.01 
                 0.10 
                 Yes 
                 No 
               
               
                 E634C 
                 −0.12 
                 0.08 
                 −0.30 
                 0.09 
                 0.42 
                 0.13 
                 Yes 
                 No 
               
               
                 E634Q 
                 −0.28 
                 0.09 
                 0.79 
                 0.07 
                 0.35 
                 0.10 
                 Yes 
                 No 
               
               
                 E634G 
                 −0.12 
                 0.03 
                 0.10 
                 0.02 
                 0.33 
                 0.03 
                 Yes 
                 No 
               
               
                 E634I 
                 0.43 
                 0.13 
                 −0.05 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E634L 
                 0.12 
                 0.05 
                 −0.46 
                 0.06 
                 0.47 
                 0.19 
                 Yes 
                 No 
               
               
                 E634K 
                 0.14 
                 0.06 
                 −0.04 
                 0.07 
                 0.16 
                 0.13 
                 Yes 
                 No 
               
               
                 E634M 
                 −0.14 
                 0.08 
                 −0.22 
                 0.08 
                 0.42 
                 0.27 
                 Yes 
                 No 
               
               
                 E634F 
                 0.25 
                 0.14 
                 0.08 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E634P 
                 −0.23 
                 0.10 
                 −0.95 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E634S 
                 −0.22 
                 0.06 
                 0.07 
                 0.05 
                 0.30 
                 0.07 
                 Yes 
                 No 
               
               
                 E634* 
                 0.11 
                 0.03 
                 0.29 
                 0.03 
                 −0.34 
                 0.05 
                 Yes 
                 No 
               
               
                 E634T 
                 0.01 
                 0.09 
                 0.30 
                 0.08 
                 −0.51 
                 0.28 
                 Yes 
                 No 
               
               
                 E634W 
                 −0.46 
                 0.06 
                 0.16 
                 0.05 
                 0.45 
                 0.17 
                 Yes 
                 No 
               
               
                 E634V 
                 −0.20 
                 0.04 
                 0.26 
                 0.04 
                 0.33 
                 0.08 
                 Yes 
                 No 
               
               
                 P635A 
                 0.04 
                 0.05 
                 0.29 
                 0.05 
                 0.59 
                 0.07 
                 Yes 
                 Yes 
               
               
                 P635D 
                 0.14 
                 0.09 
                 0.49 
                 0.09 
                 0.52 
                 0.14 
                 Yes 
                 Yes 
               
               
                 P635E 
                 0.51 
                 0.06 
                 0.49 
                 0.06 
                 0.70 
                 0.16 
                 Yes 
                 Yes 
               
               
                 P635T 
                 0.36 
                 0.06 
                 0.06 
                 0.06 
                 0.01 
                 0.08 
                 Yes 
                 Yes 
               
               
                 P635R 
                 −0.51 
                 0.04 
                 −0.39 
                 0.04 
                 0.24 
                 0.08 
                 Yes 
                 No 
               
               
                 P635N 
                 0.13 
                 0.14 
                 −0.31 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P635C 
                 −0.65 
                 0.10 
                 −0.70 
                 0.11 
                 0.26 
                 0.25 
                 Yes 
                 No 
               
               
                 P635Q 
                 −0.86 
                 0.12 
                 −0.40 
                 0.11 
                 0.43 
                 0.38 
                 Yes 
                 No 
               
               
                 P635G 
                 −0.01 
                 0.03 
                 −0.02 
                 0.03 
                 0.15 
                 0.06 
                 Yes 
                 No 
               
               
                 P635H 
                 −0.05 
                 0.10 
                 0.20 
                 0.09 
                 0.22 
                 0.07 
                 Yes 
                 No 
               
               
                 P635I 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.13 
                 0.37 
                 Yes 
                 No 
               
               
                 P635L 
                 −0.02 
                 0.05 
                 −0.33 
                 0.06 
                 0.22 
                 0.10 
                 Yes 
                 No 
               
               
                 P635K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.18 
                 0.41 
                 Yes 
                 No 
               
               
                 P635M 
                 0.96 
                 0.08 
                 −0.61 
                 0.12 
                 0.06 
                 0.31 
                 Yes 
                 No 
               
               
                 P635F 
                 1.00 
                 0.11 
                 0.14 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P635S 
                 −0.22 
                 0.06 
                 0.35 
                 0.05 
                 0.02 
                 0.12 
                 Yes 
                 No 
               
               
                 P635W 
                 −0.24 
                 0.06 
                 0.25 
                 0.06 
                 −0.12 
                 0.20 
                 Yes 
                 No 
               
               
                 P635Y 
                 −0.31 
                 0.15 
                 −0.01 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P635V 
                 −0.06 
                 0.05 
                 −0.29 
                 0.05 
                 0.44 
                 0.20 
                 Yes 
                 No 
               
               
                 L636A 
                 −0.52 
                 0.05 
                 −1.17 
                 0.06 
                 0.08 
                 0.11 
                 Yes 
                 No 
               
               
                 L636R 
                 −1.28 
                 0.04 
                 −1.29 
                 0.04 
                 −1.27 
                 0.08 
                 No 
                 No 
               
               
                 L636C 
                 −0.14 
                 0.07 
                 −0.19 
                 0.07 
                 −0.07 
                 0.17 
                 No 
                 No 
               
               
                 L636Q 
                 −0.25 
                 0.05 
                 −0.09 
                 0.05 
                 −0.16 
                 0.09 
                 No 
                 No 
               
               
                 L636E 
                 −1.02 
                 0.07 
                 −0.96 
                 0.07 
                 −1.27 
                 0.21 
                 No 
                 No 
               
               
                 L636G 
                 −1.44 
                 0.04 
                 −1.31 
                 0.04 
                 −1.36 
                 0.06 
                 No 
                 No 
               
               
                 L636I 
                 −0.87 
                 0.13 
                 −0.24 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L636K 
                 −0.17 
                 0.08 
                 −0.33 
                 0.09 
                 −1.00 
                 0.28 
                 No 
                 No 
               
               
                 L636M 
                 −0.40 
                 0.07 
                 −0.08 
                 0.06 
                 0.16 
                 0.16 
                 Yes 
                 No 
               
               
                 L636F 
                 −0.45 
                 0.10 
                 0.29 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L636P 
                 0.24 
                 0.05 
                 −0.84 
                 0.06 
                 −0.88 
                 0.11 
                 Yes 
                 No 
               
               
                 L636S 
                 −1.62 
                 0.07 
                 −1.47 
                 0.07 
                 −0.73 
                 0.15 
                 No 
                 No 
               
               
                 L636* 
                 −1.09 
                 0.10 
                 −1.51 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L636T 
                 0.12 
                 0.06 
                 −2.04 
                 0.13 
                 −0.41 
                 0.09 
                 Yes 
                 No 
               
               
                 L636W 
                 −0.55 
                 0.05 
                 −1.36 
                 0.06 
                 −0.68 
                 0.11 
                 No 
                 No 
               
               
                 L636V 
                 −0.35 
                 0.04 
                 −0.05 
                 0.03 
                 −0.65 
                 0.08 
                 No 
                 No 
               
               
                 E637A 
                 0.15 
                 0.04 
                 0.23 
                 0.04 
                 −0.25 
                 0.07 
                 Yes 
                 No 
               
               
                 E637R 
                 −0.23 
                 0.07 
                 1.02 
                 0.06 
                 0.18 
                 0.32 
                 Yes 
                 No 
               
               
                 E637D 
                 −0.88 
                 0.14 
                 −0.01 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E637Q 
                 0.83 
                 0.14 
                 0.47 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E637G 
                 −0.05 
                 0.04 
                 0.22 
                 0.04 
                 0.06 
                 0.05 
                 Yes 
                 No 
               
               
                 E637L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.35 
                 0.32 
                 Yes 
                 No 
               
               
                 E637K 
                 −0.33 
                 0.12 
                 −0.66 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E637M 
                 0.60 
                 0.15 
                 1.04 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E637S 
                 0.23 
                 0.10 
                 −0.55 
                 0.12 
                 0.66 
                 0.39 
                 Yes 
                 No 
               
               
                 E637* 
                 −0.03 
                 0.09 
                 0.24 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E637W 
                 −0.18 
                 0.10 
                 −0.73 
                 0.12 
                 −0.20 
                 0.34 
                 No 
                 No 
               
               
                 E637V 
                 −0.15 
                 0.07 
                 −0.36 
                 0.07 
                 −0.45 
                 0.10 
                 No 
                 No 
               
               
                 I638R 
                 −1.56 
                 0.13 
                 −0.55 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I638N 
                 0.35 
                 0.16 
                 0.42 
                 0.16 
                 −0.63 
                 0.15 
                 Yes 
                 No 
               
               
                 I638C 
                 1.11 
                 0.14 
                 −0.05 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I638L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.24 
                 0.30 
                 Yes 
                 No 
               
               
                 I638S 
                 0.04 
                 0.05 
                 0.05 
                 0.05 
                 −0.18 
                 0.05 
                 Yes 
                 No 
               
               
                 I638T 
                 −0.43 
                 0.12 
                 −0.42 
                 0.12 
                 −0.14 
                 0.18 
                 No 
                 No 
               
               
                 I638V 
                 0.39 
                 0.07 
                 −0.45 
                 0.08 
                 −0.04 
                 0.13 
                 Yes 
                 No 
               
               
                 T639G 
                 0.52 
                 0.06 
                 0.44 
                 0.06 
                 0.06 
                 0.23 
                 Yes 
                 Yes 
               
               
                 T639A 
                 0.25 
                 0.05 
                 0.47 
                 0.05 
                 −0.34 
                 0.06 
                 Yes 
                 No 
               
               
                 T639R 
                 −0.48 
                 0.10 
                 −0.68 
                 0.11 
                 −0.16 
                 0.35 
                 No 
                 No 
               
               
                 T639N 
                 0.03 
                 0.16 
                 −0.02 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T639D 
                 0.61 
                 0.17 
                 0.43 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T639E 
                 0.71 
                 0.12 
                 0.82 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T639I 
                 0.17 
                 0.13 
                 −0.19 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T639L 
                 −0.28 
                 0.15 
                 −0.39 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T639P 
                 −0.10 
                 0.12 
                 0.08 
                 0.12 
                 −0.21 
                 0.22 
                 Yes 
                 No 
               
               
                 T639S 
                 0.07 
                 0.07 
                 0.09 
                 0.07 
                 −0.53 
                 0.12 
                 Yes 
                 No 
               
               
                 T639V 
                 0.75 
                 0.09 
                 −1.09 
                 0.14 
                 0.78 
                 0.28 
                 Yes 
                 No 
               
               
                 K640A 
                 −0.31 
                 0.07 
                 −0.59 
                 0.07 
                 0.20 
                 0.26 
                 Yes 
                 No 
               
               
                 K640R 
                 −0.15 
                 0.04 
                 0.07 
                 0.04 
                 0.01 
                 0.11 
                 Yes 
                 No 
               
               
                 K640N 
                 0.07 
                 0.03 
                 0.32 
                 0.03 
                 −0.43 
                 0.05 
                 Yes 
                 No 
               
               
                 K640D 
                 −0.14 
                 0.09 
                 −0.73 
                 0.11 
                 −0.52 
                 0.30 
                 No 
                 No 
               
               
                 K640C 
                 0.06 
                 0.08 
                 0.34 
                 0.08 
                 −0.51 
                 0.27 
                 Yes 
                 No 
               
               
                 K640Q 
                 −0.86 
                 0.12 
                 0.36 
                 0.09 
                 0.29 
                 0.31 
                 Yes 
                 No 
               
               
                 K640E 
                 −0.30 
                 0.06 
                 0.08 
                 0.06 
                 −0.03 
                 0.15 
                 Yes 
                 No 
               
               
                 K640G 
                 −0.26 
                 0.04 
                 −0.59 
                 0.04 
                 −0.48 
                 0.12 
                 No 
                 No 
               
               
                 K640H 
                 0.81 
                 0.12 
                 −0.26 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K640I 
                 −0.10 
                 0.12 
                 −0.11 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K640L 
                 0.21 
                 0.06 
                 0.05 
                 0.06 
                 −0.31 
                 0.20 
                 Yes 
                 No 
               
               
                 K640M 
                 −1.04 
                 0.15 
                 0.36 
                 0.10 
                 −0.12 
                 0.31 
                 Yes 
                 No 
               
               
                 K640F 
                 0.24 
                 0.12 
                 −0.13 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K640P 
                 0.40 
                 0.09 
                 0.14 
                 0.10 
                 −0.03 
                 0.55 
                 Yes 
                 No 
               
               
                 K640S 
                 −0.60 
                 0.07 
                 0.52 
                 0.06 
                 −0.11 
                 0.22 
                 Yes 
                 No 
               
               
                 K640* 
                 −0.85 
                 0.10 
                 −0.19 
                 0.09 
                 −0.96 
                 0.21 
                 No 
                 No 
               
               
                 K640T 
                 0.10 
                 0.03 
                 0.35 
                 0.03 
                 −0.52 
                 0.06 
                 Yes 
                 No 
               
               
                 K640W 
                 −0.53 
                 0.07 
                 0.41 
                 0.06 
                 0.12 
                 0.25 
                 Yes 
                 No 
               
               
                 K640Y 
                 −0.76 
                 0.15 
                 −0.28 
                 0.14 
                 0.36 
                 0.37 
                 Yes 
                 No 
               
               
                 K640V 
                 −0.26 
                 0.05 
                 −0.56 
                 0.05 
                 0.05 
                 0.11 
                 Yes 
                 No 
               
               
                 D840S 
                 0.37 
                 0.08 
                 0.33 
                 0.08 
                 0.10 
                 0.16 
                 Yes 
                 Yes 
               
               
                 D840A 
                 −0.07 
                 0.07 
                 0.40 
                 0.06 
                 0.18 
                 0.13 
                 Yes 
                 No 
               
               
                 D840R 
                 −0.03 
                 0.05 
                 0.09 
                 0.05 
                 0.10 
                 0.33 
                 Yes 
                 No 
               
               
                 D840N 
                 −0.64 
                 0.12 
                 −0.31 
                 0.11 
                 −0.04 
                 0.16 
                 No 
                 No 
               
               
                 D840C 
                 0.62 
                 0.12 
                 −1.20 
                 0.16 
                 0.07 
                 0.48 
                 Yes 
                 No 
               
               
                 D840Q 
                 −0.22 
                 0.14 
                 −0.03 
                 0.13 
                 0.34 
                 NA 
                 Yes 
                 No 
               
               
                 D840E 
                 0.32 
                 0.07 
                 −0.07 
                 0.07 
                 0.08 
                 0.06 
                 Yes 
                 No 
               
               
                 D840G 
                 0.21 
                 0.04 
                 −0.26 
                 0.04 
                 0.02 
                 0.05 
                 Yes 
                 No 
               
               
                 D840L 
                 −0.64 
                 0.10 
                 −0.25 
                 0.09 
                 −0.27 
                 0.82 
                 No 
                 No 
               
               
                 D840K 
                 0.13 
                 0.13 
                 0.33 
                 0.12 
                 −0.03 
                 0.82 
                 Yes 
                 No 
               
               
                 D840M 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.30 
                 0.13 
                 Yes 
                 No 
               
               
                 D840P 
                 −0.09 
                 0.12 
                 −0.12 
                 0.12 
                 0.11 
                 0.82 
                 Yes 
                 No 
               
               
                 D840T 
                 −1.14 
                 0.14 
                 0.11 
                 0.10 
                 0.29 
                 0.15 
                 Yes 
                 No 
               
               
                 D840W 
                 −0.33 
                 0.09 
                 0.05 
                 0.08 
                 −0.39 
                 0.19 
                 Yes 
                 No 
               
               
                 D840Y 
                 0.13 
                 0.08 
                 0.11 
                 0.08 
                 −0.18 
                 0.11 
                 Yes 
                 No 
               
               
                 D840V 
                 0.16 
                 0.06 
                 −0.03 
                 0.06 
                 −0.10 
                 0.07 
                 Yes 
                 No 
               
               
                 E841A 
                 −0.26 
                 0.06 
                 −0.54 
                 0.06 
                 0.08 
                 0.08 
                 Yes 
                 No 
               
               
                 E841R 
                 −0.66 
                 0.06 
                 −0.57 
                 0.05 
                 −0.18 
                 0.10 
                 No 
                 No 
               
               
                 E841N 
                 0.04 
                 0.14 
                 −0.53 
                 0.15 
                 −0.14 
                 0.48 
                 Yes 
                 No 
               
               
                 E841D 
                 −0.33 
                 0.09 
                 −0.04 
                 0.08 
                 0.12 
                 0.15 
                 Yes 
                 No 
               
               
                 E841C 
                 −0.43 
                 0.13 
                 −0.39 
                 0.12 
                 −0.46 
                 0.16 
                 No 
                 No 
               
               
                 E841Q 
                 −0.64 
                 0.12 
                 −0.41 
                 0.11 
                 0.21 
                 0.14 
                 Yes 
                 No 
               
               
                 E841G 
                 0.21 
                 0.04 
                 −0.11 
                 0.04 
                 −0.04 
                 0.04 
                 Yes 
                 No 
               
               
                 E841H 
                 −0.71 
                 0.18 
                 −0.82 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E841L 
                 −1.39 
                 0.10 
                 −0.35 
                 0.07 
                 −0.41 
                 0.06 
                 No 
                 No 
               
               
                 E841K 
                 −0.55 
                 0.09 
                 −0.26 
                 0.09 
                 −0.34 
                 0.17 
                 No 
                 No 
               
               
                 E841M 
                 −1.21 
                 0.14 
                 −0.41 
                 0.11 
                 −0.24 
                 0.54 
                 No 
                 No 
               
               
                 E841P 
                 −0.22 
                 0.11 
                 −0.23 
                 0.11 
                 0.00 
                 0.08 
                 No 
                 No 
               
               
                 E841S 
                 −0.16 
                 0.07 
                 −0.22 
                 0.07 
                 0.04 
                 0.10 
                 Yes 
                 No 
               
               
                 E841* 
                 −0.19 
                 0.06 
                 −0.19 
                 0.06 
                 0.07 
                 0.03 
                 Yes 
                 No 
               
               
                 E841T 
                 0.40 
                 0.09 
                 −0.59 
                 0.10 
                 −0.27 
                 0.19 
                 Yes 
                 No 
               
               
                 E841W 
                 −1.06 
                 0.09 
                 −1.15 
                 0.09 
                 −1.11 
                 0.33 
                 No 
                 No 
               
               
                 E841V 
                 −0.99 
                 0.07 
                 −0.68 
                 0.06 
                 −0.53 
                 0.08 
                 No 
                 No 
               
               
                 A842S 
                 0.36 
                 0.06 
                 0.08 
                 0.06 
                 0.04 
                 0.10 
                 Yes 
                 Yes 
               
               
                 A842R 
                 −2.56 
                 0.11 
                 −1.06 
                 0.06 
                 −1.25 
                 0.15 
                 No 
                 No 
               
               
                 A842D 
                 −0.37 
                 0.11 
                 −1.49 
                 0.15 
                 −1.07 
                 0.19 
                 No 
                 No 
               
               
                 A842C 
                 0.15 
                 0.10 
                 −0.39 
                 0.11 
                 −0.26 
                 0.13 
                 Yes 
                 No 
               
               
                 A842E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.19 
                 0.12 
                 Yes 
                 No 
               
               
                 A842G 
                 −0.18 
                 0.04 
                 −0.18 
                 0.04 
                 −0.09 
                 0.04 
                 No 
                 No 
               
               
                 A842L 
                 −1.71 
                 0.11 
                 −1.29 
                 0.09 
                 −1.19 
                 0.33 
                 No 
                 No 
               
               
                 A842K 
                 −0.53 
                 0.13 
                 −1.41 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A842P 
                 −0.87 
                 0.10 
                 −0.94 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A842T 
                 −1.47 
                 0.11 
                 −0.57 
                 0.08 
                 −1.03 
                 0.10 
                 No 
                 No 
               
               
                 A842W 
                 −1.87 
                 0.12 
                 −1.92 
                 0.12 
                 −1.46 
                 0.40 
                 No 
                 No 
               
               
                 A842V 
                 −1.40 
                 0.08 
                 −0.77 
                 0.06 
                 −1.17 
                 0.20 
                 No 
                 No 
               
               
                 R843A 
                 −0.28 
                 0.10 
                 0.30 
                 0.09 
                 0.15 
                 0.11 
                 Yes 
                 No 
               
               
                 R843E 
                 −1.03 
                 0.17 
                 −1.31 
                 0.17 
                 0.09 
                 0.64 
                 Yes 
                 No 
               
               
                 R843G 
                 0.18 
                 0.05 
                 −0.37 
                 0.06 
                 −0.43 
                 0.07 
                 Yes 
                 No 
               
               
                 R843L 
                 −0.31 
                 0.13 
                 −0.08 
                 0.12 
                 −0.05 
                 0.30 
                 No 
                 No 
               
               
                 R843K 
                 −0.16 
                 0.13 
                 0.01 
                 0.12 
                 0.45 
                 0.16 
                 Yes 
                 No 
               
               
                 R843M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.26 
                 0.83 
                 Yes 
                 No 
               
               
                 R843S 
                 −0.08 
                 0.07 
                 0.08 
                 0.07 
                 −0.08 
                 0.10 
                 Yes 
                 No 
               
               
                 R843* 
                 −0.64 
                 0.17 
                 −0.23 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R843T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.19 
                 0.30 
                 Yes 
                 No 
               
               
                 R843W 
                 −0.99 
                 0.15 
                 0.22 
                 0.12 
                 −0.55 
                 0.14 
                 Yes 
                 No 
               
               
                 R843V 
                 −0.09 
                 0.10 
                 −0.23 
                 0.10 
                 0.04 
                 0.17 
                 Yes 
                 No 
               
               
                 A844E 
                 0.38 
                 0.10 
                 0.06 
                 0.10 
                 0.13 
                 0.21 
                 Yes 
                 Yes 
               
               
                 A844R 
                 0.45 
                 0.07 
                 −0.04 
                 0.07 
                 0.03 
                 0.37 
                 Yes 
                 No 
               
               
                 A844D 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.36 
                 0.11 
                 Yes 
                 No 
               
               
                 A844C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.02 
                 0.19 
                 Yes 
                 No 
               
               
                 A844Q 
                 −0.26 
                 0.18 
                 0.84 
                 0.15 
                 −0.11 
                 0.44 
                 Yes 
                 No 
               
               
                 A844G 
                 −0.48 
                 0.06 
                 −0.26 
                 0.05 
                 −0.01 
                 0.06 
                 No 
                 No 
               
               
                 A844L 
                 0.54 
                 0.10 
                 −0.25 
                 0.11 
                 0.18 
                 0.14 
                 Yes 
                 No 
               
               
                 A844K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.14 
                 0.27 
                 Yes 
                 No 
               
               
                 A844M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.23 
                 0.41 
                 Yes 
                 No 
               
               
                 A844P 
                 0.28 
                 0.11 
                 −1.04 
                 0.14 
                 −0.72 
                 0.25 
                 Yes 
                 No 
               
               
                 A844S 
                 −0.22 
                 0.08 
                 −0.06 
                 0.07 
                 0.17 
                 0.10 
                 Yes 
                 No 
               
               
                 A844T 
                 −0.37 
                 0.11 
                 −0.05 
                 0.10 
                 0.22 
                 0.21 
                 Yes 
                 No 
               
               
                 A844W 
                 −1.01 
                 0.13 
                 −0.64 
                 0.11 
                 −0.10 
                 NA 
                 No 
                 No 
               
               
                 A844V 
                 −0.19 
                 0.08 
                 0.12 
                 0.07 
                 0.06 
                 0.08 
                 Yes 
                 No 
               
               
                 L845A 
                 −0.70 
                 0.08 
                 −0.23 
                 0.07 
                 −0.59 
                 0.11 
                 No 
                 No 
               
               
                 L845R 
                 −2.01 
                 0.10 
                 −1.83 
                 0.09 
                 −1.29 
                 0.05 
                 No 
                 No 
               
               
                 L845C 
                 −0.27 
                 0.14 
                 −0.84 
                 0.15 
                 −0.37 
                 0.82 
                 No 
                 No 
               
               
                 L845Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.49 
                 0.25 
                 Yes 
                 No 
               
               
                 L845E 
                 −0.93 
                 0.12 
                 −1.26 
                 0.13 
                 −0.79 
                 0.48 
                 No 
                 No 
               
               
                 L845G 
                 −1.31 
                 0.06 
                 −1.09 
                 0.06 
                 −1.46 
                 0.20 
                 No 
                 No 
               
               
                 L845K 
                 −0.17 
                 0.18 
                 0.03 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L845M 
                 −0.15 
                 0.12 
                 −0.17 
                 0.12 
                 −0.20 
                 0.25 
                 No 
                 No 
               
               
                 L845P 
                 −0.64 
                 0.10 
                 −0.71 
                 0.10 
                 −0.61 
                 0.11 
                 No 
                 No 
               
               
                 L845S 
                 −1.48 
                 0.13 
                 −0.91 
                 0.10 
                 −0.82 
                 0.35 
                 No 
                 No 
               
               
                 L845T 
                 −0.85 
                 0.14 
                 0.43 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L845W 
                 −0.12 
                 0.08 
                 −1.89 
                 0.13 
                 −0.47 
                 0.33 
                 No 
                 No 
               
               
                 L845V 
                 −0.31 
                 0.06 
                 −0.80 
                 0.07 
                 −0.20 
                 0.10 
                 No 
                 No 
               
               
                 L846A 
                 −1.10 
                 0.08 
                 −0.78 
                 0.07 
                 −0.78 
                 0.82 
                 No 
                 No 
               
               
                 L846R 
                 −0.86 
                 0.06 
                 −0.85 
                 0.05 
                 −1.09 
                 0.11 
                 No 
                 No 
               
               
                 L846C 
                 −1.57 
                 0.15 
                 −1.32 
                 0.13 
                 −0.93 
                 0.14 
                 No 
                 No 
               
               
                 L846Q 
                 −1.21 
                 0.15 
                 −0.87 
                 0.13 
                 −0.99 
                 0.27 
                 No 
                 No 
               
               
                 L846E 
                 −0.34 
                 0.08 
                 −0.41 
                 0.08 
                 −0.71 
                 0.17 
                 No 
                 No 
               
               
                 L846G 
                 −1.11 
                 0.05 
                 −0.81 
                 0.05 
                 −1.29 
                 0.15 
                 No 
                 No 
               
               
                 L846I 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.11 
                 0.49 
                 Yes 
                 No 
               
               
                 L846M 
                 −0.29 
                 0.09 
                 0.19 
                 0.08 
                 −0.28 
                 0.13 
                 Yes 
                 No 
               
               
                 L846F 
                 −0.48 
                 0.14 
                 −0.27 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L846P 
                 −1.04 
                 0.10 
                 −0.74 
                 0.09 
                 −0.74 
                 0.13 
                 No 
                 No 
               
               
                 L846S 
                 −0.77 
                 0.09 
                 −0.24 
                 0.08 
                 −1.23 
                 0.37 
                 No 
                 No 
               
               
                 L846T 
                 −0.74 
                 0.12 
                 −1.37 
                 0.14 
                 −0.56 
                 0.12 
                 No 
                 No 
               
               
                 L846W 
                 −1.13 
                 0.09 
                 −0.51 
                 0.08 
                 −0.35 
                 0.06 
                 No 
                 No 
               
               
                 L846Y 
                 −0.02 
                 0.16 
                 −0.98 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L846V 
                 −1.23 
                 0.07 
                 −0.61 
                 0.06 
                 −0.40 
                 0.06 
                 No 
                 No 
               
               
                 P847A 
                 0.24 
                 0.11 
                 −1.48 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P847R 
                 −0.47 
                 0.09 
                 −0.88 
                 0.10 
                 −1.09 
                 0.26 
                 No 
                 No 
               
               
                 P847G 
                 −0.32 
                 0.07 
                 −1.12 
                 0.08 
                 −0.48 
                 0.43 
                 No 
                 No 
               
               
                 P847H 
                 −0.24 
                 0.18 
                 −0.19 
                 0.17 
                 −0.10 
                 0.18 
                 No 
                 No 
               
               
                 P847L 
                 −1.09 
                 0.12 
                 −0.92 
                 0.11 
                 −0.76 
                 0.15 
                 No 
                 No 
               
               
                 P847S 
                 −0.42 
                 0.11 
                 −0.55 
                 0.11 
                 −0.76 
                 0.23 
                 No 
                 No 
               
               
                 P847T 
                 −0.69 
                 0.19 
                 −0.89 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P847V 
                 −0.31 
                 0.12 
                 −1.08 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N848A 
                 −0.53 
                 0.11 
                 0.02 
                 0.10 
                 0.14 
                 0.43 
                 Yes 
                 No 
               
               
                 N848R 
                 −0.30 
                 0.07 
                 −0.60 
                 0.07 
                 −0.35 
                 0.10 
                 No 
                 No 
               
               
                 N848D 
                 0.06 
                 0.11 
                 −0.08 
                 0.11 
                 −0.13 
                 0.15 
                 Yes 
                 No 
               
               
                 N848C 
                 −0.16 
                 0.14 
                 −0.15 
                 0.14 
                 −0.31 
                 NA 
                 No 
                 No 
               
               
                 N848Q 
                 −0.31 
                 0.18 
                 −0.55 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N848E 
                 −0.64 
                 0.11 
                 0.35 
                 0.09 
                 0.48 
                 0.09 
                 Yes 
                 No 
               
               
                 N848G 
                 −0.87 
                 0.07 
                 −0.40 
                 0.06 
                 −0.33 
                 0.11 
                 No 
                 No 
               
               
                 N848H 
                 −0.07 
                 0.05 
                 0.05 
                 0.05 
                 −0.06 
                 0.05 
                 Yes 
                 No 
               
               
                 N848I 
                 0.00 
                 0.17 
                 −0.09 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N848L 
                 0.08 
                 0.10 
                 −1.50 
                 0.14 
                 −0.10 
                 NA 
                 Yes 
                 No 
               
               
                 N848K 
                 −0.25 
                 0.14 
                 −0.45 
                 0.14 
                 −0.20 
                 0.19 
                 No 
                 No 
               
               
                 N848M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.10 
                 0.64 
                 Yes 
                 No 
               
               
                 N848S 
                 −0.89 
                 0.10 
                 −0.37 
                 0.08 
                 −0.30 
                 0.16 
                 No 
                 No 
               
               
                 N848T 
                 0.37 
                 0.12 
                 −0.11 
                 0.12 
                 −0.17 
                 0.11 
                 Yes 
                 No 
               
               
                 N848W 
                 −0.76 
                 0.12 
                 −0.04 
                 0.10 
                 0.22 
                 0.40 
                 Yes 
                 No 
               
               
                 N848Y 
                 −0.61 
                 0.18 
                 0.16 
                 0.16 
                 −0.20 
                 0.24 
                 Yes 
                 No 
               
               
                 N848V 
                 −0.51 
                 0.09 
                 −0.84 
                 0.10 
                 −0.29 
                 0.64 
                 No 
                 No 
               
               
                 V849A 
                 −0.93 
                 0.12 
                 0.41 
                 0.09 
                 −0.39 
                 0.18 
                 Yes 
                 No 
               
               
                 V849R 
                 −1.79 
                 0.16 
                 −1.96 
                 0.16 
                 −1.01 
                 0.29 
                 No 
                 No 
               
               
                 V849G 
                 −1.07 
                 0.08 
                 −1.40 
                 0.08 
                 −1.48 
                 0.05 
                 No 
                 No 
               
               
                 V849L 
                 0.90 
                 0.09 
                 −0.43 
                 0.11 
                 −0.12 
                 0.13 
                 Yes 
                 No 
               
               
                 V849M 
                 −0.12 
                 0.12 
                 −0.31 
                 0.12 
                 −0.19 
                 0.19 
                 No 
                 No 
               
               
                 I850A 
                 0.25 
                 0.05 
                 −0.76 
                 0.06 
                 −0.17 
                 0.06 
                 Yes 
                 No 
               
               
                 I850R 
                 −0.32 
                 0.04 
                 −0.27 
                 0.04 
                 −0.21 
                 0.06 
                 No 
                 No 
               
               
                 I850N 
                 −0.38 
                 0.13 
                 −0.44 
                 0.13 
                 −0.50 
                 0.10 
                 No 
                 No 
               
               
                 I850D 
                 −1.19 
                 0.12 
                 −0.73 
                 0.10 
                 −0.71 
                 0.54 
                 No 
                 No 
               
               
                 I850C 
                 −0.30 
                 0.08 
                 0.19 
                 0.08 
                 0.13 
                 0.14 
                 Yes 
                 No 
               
               
                 I850Q 
                 −0.08 
                 0.11 
                 −0.31 
                 0.11 
                 0.00 
                 0.43 
                 No 
                 No 
               
               
                 I850E 
                 −0.24 
                 0.07 
                 −0.45 
                 0.07 
                 −0.35 
                 0.25 
                 No 
                 No 
               
               
                 I850G 
                 −0.90 
                 0.04 
                 −0.86 
                 0.04 
                 −0.96 
                 0.06 
                 No 
                 No 
               
               
                 I850H 
                 0.45 
                 0.12 
                 −0.44 
                 0.13 
                 −0.29 
                 0.54 
                 Yes 
                 No 
               
               
                 I850L 
                 −0.15 
                 0.04 
                 −0.17 
                 0.04 
                 −0.26 
                 0.05 
                 No 
                 No 
               
               
                 I850K 
                 −1.20 
                 0.13 
                 −0.19 
                 0.10 
                 −0.01 
                 0.82 
                 No 
                 No 
               
               
                 I850M 
                 −0.83 
                 0.09 
                 −0.82 
                 0.09 
                 −0.28 
                 0.18 
                 No 
                 No 
               
               
                 I850F 
                 −0.83 
                 0.11 
                 −0.97 
                 0.11 
                 −0.61 
                 0.17 
                 No 
                 No 
               
               
                 I850P 
                 −0.43 
                 0.09 
                 −1.72 
                 0.12 
                 −1.01 
                 0.12 
                 No 
                 No 
               
               
                 I850S 
                 −0.42 
                 0.06 
                 −0.18 
                 0.05 
                 −0.52 
                 0.06 
                 No 
                 No 
               
               
                 I850T 
                 0.00 
                 0.07 
                 −0.22 
                 0.07 
                 0.06 
                 0.07 
                 Yes 
                 No 
               
               
                 I850W 
                 −1.02 
                 0.07 
                 −1.26 
                 0.08 
                 −0.97 
                 0.10 
                 No 
                 No 
               
               
                 I850V 
                 −0.03 
                 0.04 
                 0.12 
                 0.04 
                 0.22 
                 0.05 
                 Yes 
                 No 
               
               
                 T851A 
                 0.41 
                 0.06 
                 0.14 
                 0.06 
                 0.08 
                 0.10 
                 Yes 
                 Yes 
               
               
                 T851V 
                 0.32 
                 0.06 
                 0.13 
                 0.06 
                 0.54 
                 0.07 
                 Yes 
                 Yes 
               
               
                 T851R 
                 −0.18 
                 0.06 
                 −0.82 
                 0.06 
                 −0.93 
                 0.17 
                 No 
                 No 
               
               
                 T851C 
                 0.00 
                 0.14 
                 −0.03 
                 0.14 
                 −0.11 
                 0.82 
                 No 
                 No 
               
               
                 T851Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.17 
                 0.29 
                 Yes 
                 No 
               
               
                 T851E 
                 −0.44 
                 0.09 
                 −0.88 
                 0.10 
                 −0.08 
                 0.08 
                 No 
                 No 
               
               
                 T851G 
                 −1.22 
                 0.06 
                 −0.82 
                 0.05 
                 −0.95 
                 0.19 
                 No 
                 No 
               
               
                 T851I 
                 0.21 
                 0.13 
                 −0.17 
                 0.13 
                 0.20 
                 0.20 
                 Yes 
                 No 
               
               
                 T851L 
                 0.35 
                 0.08 
                 0.01 
                 0.09 
                 −0.05 
                 0.37 
                 Yes 
                 No 
               
               
                 T851K 
                 −0.23 
                 0.14 
                 −0.49 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T851M 
                 0.52 
                 0.11 
                 −0.71 
                 0.14 
                 −0.02 
                 0.23 
                 Yes 
                 No 
               
               
                 T851F 
                 −0.32 
                 0.18 
                 0.44 
                 0.16 
                 0.28 
                 NA 
                 Yes 
                 No 
               
               
                 T851P 
                 −0.06 
                 0.04 
                 0.04 
                 0.04 
                 0.03 
                 0.05 
                 Yes 
                 No 
               
               
                 T851S 
                 −0.01 
                 0.07 
                 −0.04 
                 0.07 
                 −0.08 
                 0.13 
                 No 
                 No 
               
               
                 T851W 
                 0.07 
                 0.09 
                 −0.34 
                 0.09 
                 −0.01 
                 0.48 
                 Yes 
                 No 
               
               
                 K852A 
                 −1.49 
                 0.14 
                 −1.41 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K852R 
                 −0.07 
                 0.06 
                 −0.48 
                 0.07 
                 −0.37 
                 0.10 
                 No 
                 No 
               
               
                 K852N 
                 0.12 
                 0.10 
                 −0.39 
                 0.11 
                 0.01 
                 0.08 
                 Yes 
                 No 
               
               
                 K852Q 
                 −0.04 
                 0.05 
                 0.10 
                 0.04 
                 0.14 
                 0.06 
                 Yes 
                 No 
               
               
                 K852E 
                 −0.99 
                 0.12 
                 −0.80 
                 0.11 
                 −1.03 
                 0.07 
                 No 
                 No 
               
               
                 K852G 
                 −1.42 
                 0.09 
                 −2.60 
                 0.13 
                 −1.20 
                 0.18 
                 No 
                 No 
               
               
                 K852P 
                 −0.25 
                 0.07 
                 −0.24 
                 0.07 
                 −0.22 
                 0.08 
                 No 
                 No 
               
               
                 K852S 
                 −1.14 
                 0.13 
                 −0.56 
                 0.10 
                 −0.56 
                 0.48 
                 No 
                 No 
               
               
                 K852* 
                 −0.98 
                 0.15 
                 −1.24 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K852T 
                 −0.16 
                 0.03 
                 −0.02 
                 0.03 
                 0.16 
                 0.04 
                 Yes 
                 No 
               
               
                 K852V 
                 −0.65 
                 0.09 
                 −0.18 
                 0.08 
                 −0.78 
                 0.48 
                 No 
                 No 
               
               
                 E853V 
                 0.14 
                 0.07 
                 0.10 
                 0.07 
                 0.38 
                 0.09 
                 Yes 
                 Yes 
               
               
                 E853A 
                 −0.49 
                 0.08 
                 −0.35 
                 0.08 
                 −0.05 
                 0.09 
                 No 
                 No 
               
               
                 E853R 
                 0.23 
                 0.06 
                 −0.13 
                 0.06 
                 −0.20 
                 0.31 
                 Yes 
                 No 
               
               
                 E853D 
                 −0.30 
                 0.10 
                 −0.26 
                 0.10 
                 0.42 
                 0.18 
                 Yes 
                 No 
               
               
                 E853C 
                 0.07 
                 0.11 
                 0.12 
                 0.11 
                 −0.24 
                 0.13 
                 Yes 
                 No 
               
               
                 E853Q 
                 −0.55 
                 0.17 
                 0.09 
                 0.14 
                 0.17 
                 0.31 
                 Yes 
                 No 
               
               
                 E853G 
                 −0.18 
                 0.04 
                 −0.41 
                 0.05 
                 −0.47 
                 0.07 
                 No 
                 No 
               
               
                 E853L 
                 −0.85 
                 0.10 
                 0.03 
                 0.08 
                 0.08 
                 0.08 
                 Yes 
                 No 
               
               
                 E853K 
                 0.05 
                 0.12 
                 −0.95 
                 0.15 
                 0.21 
                 0.20 
                 Yes 
                 No 
               
               
                 E853M 
                 −0.08 
                 0.15 
                 −0.94 
                 0.17 
                 0.01 
                 0.11 
                 Yes 
                 No 
               
               
                 E853P 
                 0.46 
                 0.13 
                 −0.02 
                 0.14 
                 0.28 
                 0.40 
                 Yes 
                 No 
               
               
                 E853S 
                 −0.30 
                 0.09 
                 −0.41 
                 0.09 
                 0.07 
                 0.15 
                 Yes 
                 No 
               
               
                 E853* 
                 −0.52 
                 0.09 
                 −0.38 
                 0.09 
                 −0.25 
                 0.08 
                 No 
                 No 
               
               
                 E853T 
                 −0.33 
                 0.15 
                 −0.61 
                 0.15 
                 0.57 
                 0.25 
                 Yes 
                 No 
               
               
                 E853W 
                 0.25 
                 0.08 
                 −1.68 
                 0.12 
                 −0.52 
                 0.14 
                 Yes 
                 No 
               
               
                 V854A 
                 −0.95 
                 0.08 
                 −0.31 
                 0.06 
                 −0.94 
                 0.15 
                 No 
                 No 
               
               
                 V854R 
                 −1.42 
                 0.07 
                 −1.14 
                 0.06 
                 −1.31 
                 0.13 
                 No 
                 No 
               
               
                 V854D 
                 −0.58 
                 0.13 
                 −1.22 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V854C 
                 −0.91 
                 0.13 
                 −0.17 
                 0.11 
                 −0.54 
                 0.35 
                 No 
                 No 
               
               
                 V854E 
                 −1.32 
                 0.11 
                 −1.01 
                 0.09 
                 −1.15 
                 0.18 
                 No 
                 No 
               
               
                 V854G 
                 −1.40 
                 0.06 
                 −1.44 
                 0.06 
                 −1.28 
                 0.09 
                 No 
                 No 
               
               
                 V854L 
                 −1.49 
                 0.10 
                 −0.60 
                 0.07 
                 −1.28 
                 0.13 
                 No 
                 No 
               
               
                 V854M 
                 −1.32 
                 0.13 
                 −1.02 
                 0.11 
                 −0.94 
                 0.16 
                 No 
                 No 
               
               
                 V854P 
                 −1.29 
                 0.16 
                 −1.22 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V854S 
                 −1.58 
                 0.12 
                 −0.89 
                 0.09 
                 −1.26 
                 0.21 
                 No 
                 No 
               
               
                 V854W 
                 −1.48 
                 0.10 
                 −0.37 
                 0.07 
                 −1.34 
                 0.06 
                 No 
                 No 
               
               
                 S855A 
                 0.70 
                 0.10 
                 −0.77 
                 0.12 
                 0.01 
                 0.40 
                 Yes 
                 No 
               
               
                 S855R 
                 0.40 
                 0.10 
                 −0.66 
                 0.11 
                 0.61 
                 0.12 
                 Yes 
                 No 
               
               
                 S855C 
                 −0.24 
                 0.17 
                 0.37 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S855G 
                 0.01 
                 0.07 
                 −0.69 
                 0.08 
                 −0.49 
                 0.48 
                 Yes 
                 No 
               
               
                 S855L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.20 
                 0.82 
                 Yes 
                 No 
               
               
                 S855F 
                 −0.02 
                 0.17 
                 0.31 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S855P 
                 −0.31 
                 0.12 
                 0.14 
                 0.10 
                 −0.08 
                 0.16 
                 Yes 
                 No 
               
               
                 S855T 
                 0.53 
                 0.13 
                 −0.42 
                 0.15 
                 0.41 
                 0.24 
                 Yes 
                 No 
               
               
                 S855Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.21 
                 0.29 
                 Yes 
                 No 
               
               
                 S855V 
                 0.17 
                 0.13 
                 0.00 
                 0.14 
                 0.24 
                 0.82 
                 Yes 
                 No 
               
               
                 H856R 
                 −0.04 
                 0.07 
                 −0.29 
                 0.07 
                 −0.62 
                 0.16 
                 No 
                 No 
               
               
                 H856N 
                 −1.01 
                 0.17 
                 −0.62 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H856E 
                 −0.49 
                 0.12 
                 −0.23 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H856G 
                 −0.96 
                 0.07 
                 −1.35 
                 0.07 
                 −1.43 
                 0.08 
                 No 
                 No 
               
               
                 H856L 
                 −0.83 
                 0.12 
                 −0.29 
                 0.10 
                 −0.42 
                 0.20 
                 No 
                 No 
               
               
                 H856P 
                 −0.26 
                 0.09 
                 0.07 
                 0.09 
                 −0.29 
                 0.09 
                 Yes 
                 No 
               
               
                 H856S 
                 −1.39 
                 0.17 
                 −0.13 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 H856W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.62 
                 0.17 
                 Yes 
                 No 
               
               
                 H856Y 
                 −0.65 
                 0.16 
                 −0.05 
                 0.13 
                 0.50 
                 0.20 
                 Yes 
                 No 
               
               
                 H856V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.60 
                 0.21 
                 Yes 
                 No 
               
               
                 E857A 
                 −0.23 
                 0.05 
                 −0.30 
                 0.05 
                 −0.51 
                 0.06 
                 No 
                 No 
               
               
                 E857R 
                 −0.92 
                 0.06 
                 −1.30 
                 0.06 
                 −1.05 
                 0.13 
                 No 
                 No 
               
               
                 E857D 
                 0.50 
                 0.09 
                 −0.31 
                 0.10 
                 −1.09 
                 0.21 
                 Yes 
                 No 
               
               
                 E857C 
                 −0.44 
                 0.13 
                 −1.14 
                 0.15 
                 −0.59 
                 0.40 
                 No 
                 No 
               
               
                 E857Q 
                 −0.89 
                 0.14 
                 −1.04 
                 0.14 
                 −0.73 
                 0.29 
                 No 
                 No 
               
               
                 E857G 
                 −0.98 
                 0.04 
                 −0.90 
                 0.04 
                 −1.19 
                 0.03 
                 No 
                 No 
               
               
                 E857L 
                 −0.09 
                 0.08 
                 −0.75 
                 0.09 
                 −0.99 
                 0.22 
                 No 
                 No 
               
               
                 E857K 
                 0.23 
                 0.09 
                 −0.93 
                 0.11 
                 −0.76 
                 0.14 
                 Yes 
                 No 
               
               
                 E857M 
                 −0.36 
                 0.13 
                 −0.31 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E857P 
                 −0.10 
                 0.11 
                 −0.53 
                 0.12 
                 −0.58 
                 0.54 
                 No 
                 No 
               
               
                 E857S 
                 −0.17 
                 0.08 
                 −0.67 
                 0.08 
                 −0.71 
                 0.16 
                 No 
                 No 
               
               
                 E857* 
                 −1.28 
                 0.15 
                 −0.53 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E857T 
                 −1.10 
                 0.14 
                 0.08 
                 0.10 
                 −0.09 
                 0.54 
                 Yes 
                 No 
               
               
                 E857W 
                 −0.75 
                 0.08 
                 −1.02 
                 0.08 
                 −1.03 
                 0.15 
                 No 
                 No 
               
               
                 E857V 
                 −0.10 
                 0.05 
                 −0.43 
                 0.05 
                 −0.29 
                 0.08 
                 No 
                 No 
               
               
                 I858R 
                 −1.30 
                 0.11 
                 −1.37 
                 0.10 
                 −1.32 
                 0.24 
                 No 
                 No 
               
               
                 I858G 
                 −2.03 
                 0.11 
                 −0.89 
                 0.07 
                 −1.33 
                 0.09 
                 No 
                 No 
               
               
                 I858L 
                 −0.32 
                 0.08 
                 −0.64 
                 0.08 
                 −0.25 
                 0.08 
                 No 
                 No 
               
               
                 I858F 
                 −0.53 
                 0.17 
                 −0.64 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I858S 
                 −1.55 
                 0.16 
                 −0.66 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I858T 
                 −0.49 
                 0.13 
                 −0.72 
                 0.13 
                 −0.26 
                 0.20 
                 No 
                 No 
               
               
                 I858V 
                 −0.43 
                 0.08 
                 −0.43 
                 0.08 
                 −0.69 
                 0.11 
                 No 
                 No 
               
               
                 I859A 
                 −2.25 
                 0.14 
                 −1.44 
                 0.10 
                 −0.96 
                 0.35 
                 No 
                 No 
               
               
                 I859R 
                 −1.46 
                 0.08 
                 −1.27 
                 0.07 
                 −1.13 
                 0.07 
                 No 
                 No 
               
               
                 I859N 
                 −0.63 
                 0.17 
                 −0.59 
                 0.16 
                 −0.31 
                 0.21 
                 No 
                 No 
               
               
                 I859D 
                 −1.17 
                 0.15 
                 −1.53 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I859Q 
                 −0.35 
                 0.17 
                 0.41 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I859E 
                 −0.25 
                 0.09 
                 −0.09 
                 0.08 
                 −0.48 
                 0.11 
                 No 
                 No 
               
               
                 I859G 
                 −1.65 
                 0.07 
                 −1.30 
                 0.06 
                 −1.32 
                 0.22 
                 No 
                 No 
               
               
                 I859L 
                 −0.20 
                 0.04 
                 −0.01 
                 0.04 
                 −0.26 
                 0.04 
                 No 
                 No 
               
               
                 I859M 
                 −0.66 
                 0.12 
                 0.38 
                 0.10 
                 −0.64 
                 0.11 
                 Yes 
                 No 
               
               
                 I859F 
                 −0.18 
                 0.12 
                 −0.15 
                 0.12 
                 −0.59 
                 0.12 
                 No 
                 No 
               
               
                 I859S 
                 −0.34 
                 0.08 
                 −1.05 
                 0.09 
                 −1.12 
                 0.17 
                 No 
                 No 
               
               
                 I859T 
                 −0.26 
                 0.09 
                 −0.27 
                 0.09 
                 −0.35 
                 0.15 
                 No 
                 No 
               
               
                 I859W 
                 −1.84 
                 0.15 
                 −0.31 
                 0.09 
                 −0.74 
                 0.64 
                 No 
                 No 
               
               
                 I859V 
                 0.30 
                 0.04 
                 −0.13 
                 0.05 
                 0.24 
                 0.05 
                 Yes 
                 No 
               
               
                 K860A 
                 −0.50 
                 0.06 
                 −0.35 
                 0.06 
                 −1.06 
                 0.07 
                 No 
                 No 
               
               
                 K860R 
                 −0.39 
                 0.05 
                 −0.83 
                 0.05 
                 −0.83 
                 0.10 
                 No 
                 No 
               
               
                 K860N 
                 −0.63 
                 0.12 
                 −1.47 
                 0.14 
                 −0.88 
                 0.16 
                 No 
                 No 
               
               
                 K860C 
                 −0.36 
                 0.10 
                 −0.81 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K860Q 
                 −0.18 
                 0.04 
                 −0.19 
                 0.04 
                 −0.15 
                 0.06 
                 No 
                 No 
               
               
                 K860E 
                 −0.89 
                 0.06 
                 −1.15 
                 0.07 
                 −1.08 
                 0.05 
                 No 
                 No 
               
               
                 K860G 
                 −1.23 
                 0.05 
                 −1.22 
                 0.05 
                 −1.28 
                 0.06 
                 No 
                 No 
               
               
                 K860L 
                 −0.68 
                 0.07 
                 −1.58 
                 0.09 
                 −1.19 
                 0.11 
                 No 
                 No 
               
               
                 K860M 
                 −0.24 
                 0.09 
                 −0.56 
                 0.09 
                 −1.00 
                 0.15 
                 No 
                 No 
               
               
                 K860P 
                 −0.21 
                 0.07 
                 −0.49 
                 0.07 
                 −0.50 
                 0.09 
                 No 
                 No 
               
               
                 K860S 
                 −1.38 
                 0.08 
                 −1.80 
                 0.09 
                 −1.30 
                 0.07 
                 No 
                 No 
               
               
                 K860* 
                 −1.43 
                 0.12 
                 −1.23 
                 0.11 
                 −1.17 
                 0.16 
                 No 
                 No 
               
               
                 K860T 
                 −0.15 
                 0.04 
                 −0.15 
                 0.04 
                 −0.07 
                 0.06 
                 No 
                 No 
               
               
                 K860W 
                 −1.18 
                 0.08 
                 −1.46 
                 0.09 
                 −1.24 
                 0.09 
                 No 
                 No 
               
               
                 K860V 
                 −0.88 
                 0.06 
                 −1.87 
                 0.08 
                 −1.03 
                 0.04 
                 No 
                 No 
               
               
                 D861A 
                 −0.47 
                 0.05 
                 −0.76 
                 0.06 
                 −1.12 
                 0.11 
                 No 
                 No 
               
               
                 D861R 
                 −1.43 
                 0.06 
                 −1.83 
                 0.06 
                 −1.24 
                 0.09 
                 No 
                 No 
               
               
                 D861N 
                 −0.46 
                 0.10 
                 −0.59 
                 0.10 
                 −0.60 
                 0.17 
                 No 
                 No 
               
               
                 D861C 
                 −0.40 
                 0.08 
                 −0.50 
                 0.08 
                 −0.69 
                 0.08 
                 No 
                 No 
               
               
                 D861Q 
                 −0.65 
                 0.11 
                 0.09 
                 0.09 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D861E 
                 −0.97 
                 0.07 
                 −0.89 
                 0.06 
                 −0.50 
                 0.12 
                 No 
                 No 
               
               
                 D861G 
                 −0.85 
                 0.03 
                 −1.00 
                 0.03 
                 −1.03 
                 0.03 
                 No 
                 No 
               
               
                 D861H 
                 0.92 
                 0.12 
                 −0.60 
                 0.15 
                 −0.36 
                 0.21 
                 Yes 
                 No 
               
               
                 D861L 
                 −0.37 
                 0.07 
                 0.09 
                 0.06 
                 −0.18 
                 0.27 
                 Yes 
                 No 
               
               
                 D861K 
                 0.55 
                 0.09 
                 −1.49 
                 0.13 
                 −1.22 
                 0.43 
                 Yes 
                 No 
               
               
                 D861M 
                 −0.29 
                 0.10 
                 −0.57 
                 0.10 
                 −0.68 
                 0.40 
                 No 
                 No 
               
               
                 D861F 
                 −1.05 
                 0.15 
                 −0.55 
                 0.13 
                 −0.22 
                 0.12 
                 No 
                 No 
               
               
                 D861S 
                 −1.43 
                 0.09 
                 −1.60 
                 0.09 
                 −1.45 
                 0.28 
                 No 
                 No 
               
               
                 D861W 
                 −0.88 
                 0.07 
                 −0.84 
                 0.07 
                 −0.15 
                 0.08 
                 No 
                 No 
               
               
                 D861Y 
                 −0.18 
                 0.17 
                 0.14 
                 0.16 
                 −0.35 
                 0.14 
                 Yes 
                 No 
               
               
                 D861V 
                 −1.18 
                 0.06 
                 −0.99 
                 0.05 
                 −1.28 
                 0.12 
                 No 
                 No 
               
               
                 R862K 
                 0.04 
                 0.14 
                 0.54 
                 0.13 
                 0.02 
                 0.38 
                 Yes 
                 Yes 
               
               
                 R862A 
                 −1.76 
                 0.13 
                 −0.42 
                 0.08 
                 −0.71 
                 0.31 
                 No 
                 No 
               
               
                 R862C 
                 −0.64 
                 0.12 
                 −1.78 
                 0.16 
                 −0.65 
                 0.28 
                 No 
                 No 
               
               
                 R862Q 
                 −0.27 
                 0.10 
                 −0.07 
                 0.09 
                 −0.28 
                 0.13 
                 No 
                 No 
               
               
                 R862E 
                 −0.64 
                 0.12 
                 −1.63 
                 0.15 
                 −0.76 
                 0.09 
                 No 
                 No 
               
               
                 R862G 
                 −0.72 
                 0.05 
                 −0.83 
                 0.05 
                 −0.85 
                 0.07 
                 No 
                 No 
               
               
                 R862L 
                 −0.90 
                 0.08 
                 −0.16 
                 0.07 
                 −0.39 
                 0.09 
                 No 
                 No 
               
               
                 R862M 
                 −1.06 
                 0.17 
                 −0.69 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R862P 
                 −1.33 
                 0.17 
                 −1.10 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R862W 
                 −1.35 
                 0.11 
                 −0.91 
                 0.09 
                 −1.10 
                 0.14 
                 No 
                 No 
               
               
                 R862V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.61 
                 0.43 
                 Yes 
                 No 
               
               
                 R863Q 
                 −0.49 
                 0.13 
                 −0.79 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R863G 
                 −1.68 
                 0.09 
                 −1.14 
                 0.07 
                 −1.45 
                 0.07 
                 No 
                 No 
               
               
                 R863L 
                 −1.18 
                 0.15 
                 −1.68 
                 0.17 
                 −1.02 
                 0.13 
                 No 
                 No 
               
               
                 R863W 
                 −1.27 
                 0.11 
                 −1.06 
                 0.10 
                 −1.17 
                 0.14 
                 No 
                 No 
               
               
                 F864I 
                 −0.25 
                 0.11 
                 −0.08 
                 0.11 
                 −0.19 
                 0.12 
                 No 
                 No 
               
               
                 F864L 
                 0.01 
                 0.07 
                 −0.06 
                 0.07 
                 0.06 
                 0.08 
                 Yes 
                 No 
               
               
                 F864S 
                 −0.34 
                 0.14 
                 −0.27 
                 0.14 
                 −0.35 
                 0.17 
                 No 
                 No 
               
               
                 F864W 
                 −0.66 
                 0.18 
                 −0.77 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F864V 
                 −0.11 
                 0.06 
                 −0.13 
                 0.05 
                 0.00 
                 0.08 
                 No 
                 No 
               
               
                 T865A 
                 −0.65 
                 0.14 
                 −0.29 
                 0.12 
                 −0.09 
                 0.18 
                 No 
                 No 
               
               
                 T865N 
                 0.07 
                 0.03 
                 −0.05 
                 0.03 
                 −0.15 
                 0.04 
                 Yes 
                 No 
               
               
                 T865I 
                 −0.01 
                 0.10 
                 0.20 
                 0.09 
                 0.20 
                 0.13 
                 Yes 
                 No 
               
               
                 T865L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.57 
                 0.29 
                 Yes 
                 No 
               
               
                 T865P 
                 −0.10 
                 0.05 
                 −0.07 
                 0.05 
                 −0.01 
                 0.06 
                 No 
                 No 
               
               
                 T865S 
                 −0.20 
                 0.02 
                 −0.20 
                 0.02 
                 0.01 
                 0.03 
                 Yes 
                 No 
               
               
                 T865Y 
                 −0.16 
                 0.06 
                 −0.17 
                 0.05 
                 −0.16 
                 0.10 
                 No 
                 No 
               
               
                 S866F 
                 0.00 
                 0.13 
                 0.06 
                 0.12 
                 0.10 
                 0.14 
                 Yes 
                 Yes 
               
               
                 S866T 
                 0.05 
                 0.13 
                 0.02 
                 0.13 
                 0.40 
                 0.15 
                 Yes 
                 Yes 
               
               
                 S866A 
                 −0.10 
                 0.09 
                 −0.40 
                 0.10 
                 0.05 
                 0.07 
                 Yes 
                 No 
               
               
                 S866R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.33 
                 0.09 
                 Yes 
                 No 
               
               
                 S866D 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.02 
                 0.24 
                 Yes 
                 No 
               
               
                 S866C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.05 
                 0.43 
                 Yes 
                 No 
               
               
                 S866Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.04 
                 0.27 
                 Yes 
                 No 
               
               
                 S866E 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.58 
                 0.22 
                 Yes 
                 No 
               
               
                 S866G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.97 
                 0.29 
                 Yes 
                 No 
               
               
                 S866L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.57 
                 0.10 
                 Yes 
                 No 
               
               
                 S866M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.85 
                 0.14 
                 Yes 
                 No 
               
               
                 S866P 
                 0.08 
                 0.03 
                 −0.07 
                 0.03 
                 0.00 
                 0.03 
                 Yes 
                 No 
               
               
                 S866W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.67 
                 0.37 
                 Yes 
                 No 
               
               
                 S866Y 
                 0.13 
                 0.16 
                 −0.17 
                 0.17 
                 0.03 
                 0.11 
                 Yes 
                 No 
               
               
                 S866V 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.00 
                 0.08 
                 Yes 
                 No 
               
               
                 D867A 
                 0.05 
                 0.02 
                 −0.05 
                 0.02 
                 −0.05 
                 0.02 
                 Yes 
                 No 
               
               
                 D867R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.39 
                 0.06 
                 Yes 
                 No 
               
               
                 D867N 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.17 
                 0.14 
                 Yes 
                 No 
               
               
                 D867C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.98 
                 0.17 
                 Yes 
                 No 
               
               
                 D867E 
                 −0.16 
                 0.11 
                 −0.21 
                 0.11 
                 −0.99 
                 0.09 
                 No 
                 No 
               
               
                 D867G 
                 0.06 
                 0.02 
                 0.00 
                 0.02 
                 −0.11 
                 0.02 
                 Yes 
                 No 
               
               
                 D867H 
                 −0.04 
                 0.09 
                 0.11 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D867S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.98 
                 0.09 
                 Yes 
                 No 
               
               
                 D867W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.25 
                 0.13 
                 Yes 
                 No 
               
               
                 D867Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.02 
                 0.12 
                 Yes 
                 No 
               
               
                 D867V 
                 −0.04 
                 0.10 
                 −0.07 
                 0.10 
                 −0.92 
                 0.07 
                 No 
                 No 
               
               
                 K868A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.23 
                 0.28 
                 Yes 
                 No 
               
               
                 K868R 
                 −0.01 
                 0.02 
                 0.02 
                 0.02 
                 −0.76 
                 0.04 
                 Yes 
                 No 
               
               
                 K868N 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.00 
                 0.11 
                 Yes 
                 No 
               
               
                 K868Q 
                 −0.14 
                 0.09 
                 −0.02 
                 0.09 
                 −0.11 
                 0.08 
                 No 
                 No 
               
               
                 K868E 
                 −0.43 
                 0.19 
                 −0.52 
                 0.19 
                 −1.33 
                 0.19 
                 No 
                 No 
               
               
                 K868G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.49 
                 0.08 
                 Yes 
                 No 
               
               
                 K868P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.00 
                 0.09 
                 Yes 
                 No 
               
               
                 K868S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.32 
                 0.15 
                 Yes 
                 No 
               
               
                 K868* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.02 
                 0.18 
                 Yes 
                 No 
               
               
                 K868T 
                 −0.15 
                 0.03 
                 −0.12 
                 0.03 
                 −0.14 
                 0.07 
                 No 
                 No 
               
               
                 K868W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.50 
                 0.15 
                 Yes 
                 No 
               
               
                 K868V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.12 
                 0.16 
                 Yes 
                 No 
               
               
                 F869A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.10 
                 0.15 
                 Yes 
                 No 
               
               
                 F869R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.47 
                 0.27 
                 Yes 
                 No 
               
               
                 F869C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.20 
                 0.15 
                 Yes 
                 No 
               
               
                 F869E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.41 
                 0.09 
                 Yes 
                 No 
               
               
                 F869G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.40 
                 0.04 
                 Yes 
                 No 
               
               
                 F869I 
                 0.06 
                 0.10 
                 −0.10 
                 0.10 
                 0.04 
                 0.09 
                 Yes 
                 No 
               
               
                 F869L 
                 −0.16 
                 0.03 
                 −0.17 
                 0.03 
                 −0.01 
                 0.06 
                 No 
                 No 
               
               
                 F869M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.14 
                 0.09 
                 Yes 
                 No 
               
               
                 F869S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.16 
                 0.09 
                 Yes 
                 No 
               
               
                 F869W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.32 
                 0.12 
                 Yes 
                 No 
               
               
                 F869Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.21 
                 0.24 
                 Yes 
                 No 
               
               
                 F869V 
                 −0.16 
                 0.05 
                 −0.18 
                 0.05 
                 −0.62 
                 0.05 
                 No 
                 No 
               
               
                 L870A 
                 −0.86 
                 0.11 
                 −0.83 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870R 
                 −1.55 
                 0.08 
                 −1.55 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870E 
                 −1.23 
                 0.14 
                 −1.60 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870G 
                 −1.54 
                 0.07 
                 −1.47 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870M 
                 −0.94 
                 0.16 
                 −1.13 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870F 
                 −1.01 
                 0.07 
                 −0.78 
                 0.07 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870P 
                 −0.29 
                 0.06 
                 −0.36 
                 0.06 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L870V 
                 −0.67 
                 0.08 
                 −0.82 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F870A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.06 
                 0.37 
                 Yes 
                 No 
               
               
                 F870R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.61 
                 0.14 
                 Yes 
                 No 
               
               
                 F870C 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.66 
                 0.43 
                 Yes 
                 No 
               
               
                 F870G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.20 
                 0.19 
                 Yes 
                 No 
               
               
                 F870I 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.71 
                 0.17 
                 Yes 
                 No 
               
               
                 F870L 
                 NA 
                 NA 
                 NA 
                 NA 
                 1.11 
                 0.06 
                 Yes 
                 No 
               
               
                 F870M 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.04 
                 0.44 
                 Yes 
                 No 
               
               
                 F870S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.82 
                 0.17 
                 Yes 
                 No 
               
               
                 F870V 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.05 
                 0.09 
                 Yes 
                 No 
               
               
                 F871R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.55 
                 0.28 
                 Yes 
                 No 
               
               
                 F871C 
                 −0.24 
                 0.17 
                 −0.04 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F871G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.08 
                 0.22 
                 Yes 
                 No 
               
               
                 F871L 
                 −0.17 
                 0.07 
                 −0.16 
                 0.07 
                 −0.50 
                 0.08 
                 No 
                 No 
               
               
                 F871S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.74 
                 0.12 
                 Yes 
                 No 
               
               
                 F871V 
                 0.19 
                 0.12 
                 −0.06 
                 0.12 
                 −0.68 
                 0.22 
                 Yes 
                 No 
               
               
                 H872R 
                 −0.49 
                 0.19 
                 −0.27 
                 0.18 
                 −1.33 
                 0.16 
                 No 
                 No 
               
               
                 H872Q 
                 −0.40 
                 0.10 
                 −0.32 
                 0.10 
                 −0.60 
                 0.11 
                 No 
                 No 
               
               
                 H872G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.61 
                 0.11 
                 Yes 
                 No 
               
               
                 H872L 
                 0.00 
                 0.08 
                 −0.15 
                 0.08 
                 −0.43 
                 0.08 
                 No 
                 No 
               
               
                 H872P 
                 0.04 
                 0.02 
                 −0.01 
                 0.02 
                 0.34 
                 0.02 
                 Yes 
                 No 
               
               
                 H872Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.10 
                 0.21 
                 Yes 
                 No 
               
               
                 H872V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.51 
                 0.48 
                 Yes 
                 No 
               
               
                 V873A 
                 0.16 
                 0.11 
                 0.05 
                 0.11 
                 0.08 
                 0.16 
                 Yes 
                 Yes 
               
               
                 V873E 
                 −0.40 
                 0.14 
                 −0.35 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V873G 
                 −0.13 
                 0.04 
                 −0.20 
                 0.03 
                 −0.27 
                 0.07 
                 No 
                 No 
               
               
                 V873L 
                 −0.20 
                 0.05 
                 0.24 
                 0.05 
                 −0.40 
                 0.08 
                 Yes 
                 No 
               
               
                 V873M 
                 −0.48 
                 0.12 
                 −0.33 
                 0.11 
                 −0.16 
                 0.16 
                 No 
                 No 
               
               
                 P874A 
                 −0.12 
                 0.06 
                 0.06 
                 0.06 
                 0.03 
                 0.11 
                 Yes 
                 No 
               
               
                 P874G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.22 
                 0.17 
                 Yes 
                 No 
               
               
                 P874S 
                 −0.06 
                 0.10 
                 −0.17 
                 0.10 
                 0.58 
                 0.11 
                 Yes 
                 No 
               
               
                 P874T 
                 −0.23 
                 0.06 
                 −0.24 
                 0.06 
                 −0.09 
                 0.04 
                 No 
                 No 
               
               
                 I875R 
                 −0.33 
                 0.12 
                 −0.24 
                 0.11 
                 −0.82 
                 0.10 
                 No 
                 No 
               
               
                 I875N 
                 −0.01 
                 0.07 
                 −0.09 
                 0.07 
                 0.03 
                 0.08 
                 Yes 
                 No 
               
               
                 I875G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.64 
                 0.10 
                 Yes 
                 No 
               
               
                 I875H 
                 0.10 
                 0.11 
                 −0.01 
                 0.11 
                 −0.25 
                 0.11 
                 Yes 
                 No 
               
               
                 I875L 
                 0.08 
                 0.02 
                 0.02 
                 0.02 
                 −0.08 
                 0.02 
                 Yes 
                 No 
               
               
                 I875M 
                 −0.44 
                 0.17 
                 −0.26 
                 0.16 
                 0.05 
                 0.17 
                 Yes 
                 No 
               
               
                 I875F 
                 −0.20 
                 0.09 
                 −0.13 
                 0.09 
                 −0.12 
                 0.10 
                 No 
                 No 
               
               
                 I875S 
                 −0.06 
                 0.07 
                 −0.04 
                 0.07 
                 −0.22 
                 0.07 
                 No 
                 No 
               
               
                 I875T 
                 −0.01 
                 0.10 
                 −0.10 
                 0.09 
                 −0.11 
                 0.11 
                 No 
                 No 
               
               
                 I875V 
                 −0.24 
                 0.17 
                 −0.16 
                 0.16 
                 −0.44 
                 0.10 
                 No 
                 No 
               
               
                 T876A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.21 
                 0.20 
                 Yes 
                 No 
               
               
                 T876R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.72 
                 0.26 
                 Yes 
                 No 
               
               
                 T876N 
                 −0.10 
                 0.03 
                 −0.09 
                 0.03 
                 −0.07 
                 0.05 
                 No 
                 No 
               
               
                 T876G 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.44 
                 0.22 
                 Yes 
                 No 
               
               
                 T876P 
                 −0.03 
                 0.06 
                 −0.07 
                 0.06 
                 −0.30 
                 0.05 
                 No 
                 No 
               
               
                 T876S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.63 
                 0.19 
                 Yes 
                 No 
               
               
                 T876V 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.34 
                 0.33 
                 Yes 
                 No 
               
               
                 L877A 
                 0.09 
                 0.12 
                 −0.51 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877R 
                 −0.89 
                 0.08 
                 −1.39 
                 0.09 
                 −1.53 
                 0.08 
                 No 
                 No 
               
               
                 L877C 
                 −0.26 
                 0.17 
                 −0.47 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877Q 
                 −0.43 
                 0.11 
                 −0.45 
                 0.11 
                 −0.39 
                 0.13 
                 No 
                 No 
               
               
                 L877G 
                 −1.42 
                 0.09 
                 −2.38 
                 0.13 
                 −1.74 
                 0.35 
                 No 
                 No 
               
               
                 L877P 
                 −0.08 
                 0.07 
                 −0.22 
                 0.07 
                 −0.40 
                 0.12 
                 No 
                 No 
               
               
                 L877S 
                 −1.11 
                 0.16 
                 −0.99 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877V 
                 −1.25 
                 0.14 
                 0.04 
                 0.10 
                 −0.96 
                 0.08 
                 Yes 
                 No 
               
               
                 L877A 
                 −0.03 
                 0.10 
                 −0.76 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877R 
                 −0.15 
                 0.04 
                 −0.31 
                 0.04 
                 −0.02 
                 0.04 
                 No 
                 No 
               
               
                 L877C 
                 −0.29 
                 0.15 
                 −0.65 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877Q 
                 −0.26 
                 0.11 
                 −0.47 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877E 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.74 
                 0.64 
                 Yes 
                 No 
               
               
                 L877G 
                 −1.40 
                 0.08 
                 −2.82 
                 0.12 
                 −1.79 
                 0.22 
                 No 
                 No 
               
               
                 L877M 
                 −0.19 
                 0.11 
                 0.18 
                 0.10 
                 0.26 
                 0.10 
                 Yes 
                 No 
               
               
                 L877P 
                 −0.28 
                 0.09 
                 −0.39 
                 0.08 
                 −0.46 
                 0.15 
                 No 
                 No 
               
               
                 L877S 
                 −1.31 
                 0.14 
                 −1.01 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L877V 
                 −1.10 
                 0.10 
                 −0.29 
                 0.08 
                 −0.58 
                 0.06 
                 No 
                 No 
               
               
                 N878D 
                 0.03 
                 0.06 
                 0.02 
                 0.06 
                 0.04 
                 0.08 
                 Yes 
                 Yes 
               
               
                 N878A 
                 0.17 
                 0.16 
                 −0.41 
                 0.17 
                 −0.06 
                 0.25 
                 Yes 
                 No 
               
               
                 N878Q 
                 −0.22 
                 0.17 
                 −0.53 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N878E 
                 −0.73 
                 0.15 
                 −0.44 
                 0.13 
                 −0.84 
                 0.13 
                 No 
                 No 
               
               
                 N878G 
                 −0.57 
                 0.10 
                 −0.98 
                 0.11 
                 −0.70 
                 0.06 
                 No 
                 No 
               
               
                 N878H 
                 −0.01 
                 0.05 
                 −0.10 
                 0.05 
                 0.03 
                 0.05 
                 Yes 
                 No 
               
               
                 N878L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.13 
                 0.64 
                 Yes 
                 No 
               
               
                 N878K 
                 −0.01 
                 0.02 
                 −0.05 
                 0.02 
                 −0.06 
                 0.02 
                 No 
                 No 
               
               
                 N878S 
                 −1.08 
                 0.15 
                 −0.43 
                 0.12 
                 −0.38 
                 0.10 
                 No 
                 No 
               
               
                 N878T 
                 −0.16 
                 0.06 
                 0.09 
                 0.06 
                 0.15 
                 0.07 
                 Yes 
                 No 
               
               
                 N878Y 
                 −0.05 
                 0.07 
                 0.00 
                 0.06 
                 0.06 
                 0.04 
                 Yes 
                 No 
               
               
                 N878V 
                 −1.01 
                 0.17 
                 −0.32 
                 0.14 
                 −0.19 
                 0.34 
                 No 
                 No 
               
               
                 N878A 
                 0.03 
                 0.14 
                 −0.32 
                 0.14 
                 −0.19 
                 0.54 
                 Yes 
                 No 
               
               
                 N878D 
                 −0.11 
                 0.12 
                 −0.34 
                 0.12 
                 −0.62 
                 0.15 
                 No 
                 No 
               
               
                 N878C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.58 
                 0.42 
                 Yes 
                 No 
               
               
                 N878G 
                 −0.62 
                 0.10 
                 −1.09 
                 0.11 
                 −0.81 
                 0.05 
                 No 
                 No 
               
               
                 N878I 
                 −0.35 
                 0.16 
                 −0.02 
                 0.15 
                 −0.41 
                 0.17 
                 No 
                 No 
               
               
                 N878L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.12 
                 0.82 
                 Yes 
                 No 
               
               
                 N878K 
                 −0.34 
                 0.13 
                 −0.40 
                 0.13 
                 −0.39 
                 0.08 
                 No 
                 No 
               
               
                 N878M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.25 
                 0.16 
                 Yes 
                 No 
               
               
                 N878S 
                 −0.54 
                 0.11 
                 −0.30 
                 0.10 
                 −0.50 
                 0.07 
                 No 
                 No 
               
               
                 N878T 
                 −0.19 
                 0.05 
                 −0.20 
                 0.05 
                 −0.37 
                 0.09 
                 No 
                 No 
               
               
                 N878Y 
                 −0.34 
                 0.18 
                 −0.28 
                 0.17 
                 −0.12 
                 0.21 
                 No 
                 No 
               
               
                 N878V 
                 −0.98 
                 0.15 
                 −0.37 
                 0.12 
                 −0.51 
                 0.32 
                 No 
                 No 
               
               
                 Y879A 
                 −2.04 
                 0.15 
                 −1.14 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y879R 
                 −0.78 
                 0.08 
                 −1.40 
                 0.08 
                 −1.48 
                 0.11 
                 No 
                 No 
               
               
                 Y879D 
                 0.39 
                 0.05 
                 −0.19 
                 0.06 
                 −0.18 
                 0.07 
                 Yes 
                 No 
               
               
                 Y879C 
                 0.50 
                 0.06 
                 −0.02 
                 0.07 
                 −0.50 
                 0.09 
                 Yes 
                 No 
               
               
                 Y879Q 
                 −0.72 
                 0.19 
                 −0.38 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y879E 
                 −1.40 
                 0.13 
                 −1.23 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y879G 
                 −0.58 
                 0.05 
                 −1.93 
                 0.07 
                 −1.84 
                 0.23 
                 No 
                 No 
               
               
                 Y879H 
                 0.35 
                 0.09 
                 0.04 
                 0.09 
                 −0.16 
                 0.12 
                 Yes 
                 No 
               
               
                 Y879L 
                 −1.45 
                 0.13 
                 0.26 
                 0.08 
                 −1.39 
                 0.33 
                 Yes 
                 No 
               
               
                 Y879K 
                 0.13 
                 0.14 
                 −1.11 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Y879F 
                 −0.05 
                 0.12 
                 −0.01 
                 0.11 
                 0.01 
                 0.17 
                 Yes 
                 No 
               
               
                 Y879S 
                 0.37 
                 0.04 
                 −0.29 
                 0.04 
                 −0.43 
                 0.07 
                 Yes 
                 No 
               
               
                 Y879* 
                 −0.20 
                 0.11 
                 0.92 
                 0.09 
                 −0.81 
                 0.15 
                 Yes 
                 No 
               
               
                 Y879W 
                 −0.05 
                 0.08 
                 −0.07 
                 0.07 
                 0.60 
                 0.07 
                 Yes 
                 No 
               
               
                 Y879V 
                 −0.53 
                 0.08 
                 −0.97 
                 0.08 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q880R 
                 0.13 
                 0.05 
                 0.02 
                 0.05 
                 0.01 
                 0.06 
                 Yes 
                 Yes 
               
               
                 Q880G 
                 0.25 
                 0.04 
                 0.19 
                 0.04 
                 0.64 
                 0.05 
                 Yes 
                 Yes 
               
               
                 Q880A 
                 −0.10 
                 0.08 
                 0.40 
                 0.07 
                 −0.19 
                 0.20 
                 Yes 
                 No 
               
               
                 Q880D 
                 0.81 
                 0.14 
                 −1.10 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q880C 
                 −0.08 
                 0.14 
                 −1.19 
                 0.17 
                 0.17 
                 0.14 
                 Yes 
                 No 
               
               
                 Q880E 
                 −0.73 
                 0.10 
                 −1.06 
                 0.10 
                 −0.58 
                 0.08 
                 No 
                 No 
               
               
                 Q880H 
                 0.24 
                 0.08 
                 −0.08 
                 0.08 
                 −0.10 
                 0.08 
                 Yes 
                 No 
               
               
                 Q880L 
                 −0.80 
                 0.08 
                 −0.59 
                 0.07 
                 −1.39 
                 0.07 
                 No 
                 No 
               
               
                 Q880K 
                 −0.23 
                 0.13 
                 −0.27 
                 0.13 
                 −0.44 
                 0.09 
                 No 
                 No 
               
               
                 Q880M 
                 −0.93 
                 0.16 
                 −0.77 
                 0.14 
                 −0.49 
                 0.17 
                 No 
                 No 
               
               
                 Q880P 
                 −0.07 
                 0.10 
                 −0.40 
                 0.10 
                 0.12 
                 0.07 
                 Yes 
                 No 
               
               
                 Q880S 
                 −0.31 
                 0.09 
                 −0.76 
                 0.10 
                 −0.09 
                 0.07 
                 No 
                 No 
               
               
                 Q880* 
                 −1.27 
                 0.14 
                 −0.76 
                 0.11 
                 −1.05 
                 0.11 
                 No 
                 No 
               
               
                 Q880T 
                 −0.52 
                 0.14 
                 −0.18 
                 0.12 
                 0.07 
                 0.29 
                 Yes 
                 No 
               
               
                 Q880W 
                 −0.68 
                 0.08 
                 −0.91 
                 0.08 
                 −0.82 
                 0.06 
                 No 
                 No 
               
               
                 Q880V 
                 −1.77 
                 0.10 
                 −0.81 
                 0.07 
                 −0.63 
                 0.07 
                 No 
                 No 
               
               
                 A881R 
                 −0.95 
                 0.07 
                 −1.75 
                 0.08 
                 −1.43 
                 0.18 
                 No 
                 No 
               
               
                 A881D 
                 −0.36 
                 0.11 
                 −0.32 
                 0.10 
                 −0.48 
                 0.19 
                 No 
                 No 
               
               
                 A881C 
                 −0.35 
                 0.14 
                 −0.78 
                 0.15 
                 −0.49 
                 0.10 
                 No 
                 No 
               
               
                 A881G 
                 0.14 
                 0.04 
                 0.32 
                 0.04 
                 −0.41 
                 0.04 
                 Yes 
                 No 
               
               
                 A881L 
                 −1.36 
                 0.11 
                 −2.39 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A881P 
                 −1.05 
                 0.16 
                 −0.99 
                 0.14 
                 −0.80 
                 0.18 
                 No 
                 No 
               
               
                 A881S 
                 0.13 
                 0.05 
                 0.13 
                 0.05 
                 −0.13 
                 0.06 
                 Yes 
                 No 
               
               
                 A881T 
                 −0.73 
                 0.10 
                 −0.95 
                 0.10 
                 −0.44 
                 0.14 
                 No 
                 No 
               
               
                 A881W 
                 −1.25 
                 0.12 
                 −1.48 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A881V 
                 −1.66 
                 0.09 
                 −1.28 
                 0.07 
                 −0.91 
                 0.08 
                 No 
                 No 
               
               
                 A882D 
                 0.32 
                 0.05 
                 0.22 
                 0.05 
                 0.10 
                 0.07 
                 Yes 
                 Yes 
               
               
                 A882S 
                 0.11 
                 0.12 
                 0.14 
                 0.11 
                 0.23 
                 0.22 
                 Yes 
                 Yes 
               
               
                 A882R 
                 −0.10 
                 0.10 
                 0.54 
                 0.09 
                 0.51 
                 0.35 
                 Yes 
                 No 
               
               
                 A882G 
                 −0.43 
                 0.07 
                 −0.32 
                 0.06 
                 −0.14 
                 0.06 
                 No 
                 No 
               
               
                 A882L 
                 −1.02 
                 0.19 
                 0.32 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A882P 
                 −0.12 
                 0.14 
                 −0.11 
                 0.13 
                 −0.12 
                 0.24 
                 No 
                 No 
               
               
                 A882T 
                 −0.14 
                 0.09 
                 0.05 
                 0.09 
                 −0.09 
                 0.13 
                 Yes 
                 No 
               
               
                 A882V 
                 0.39 
                 0.08 
                 0.04 
                 0.08 
                 −0.17 
                 0.15 
                 Yes 
                 No 
               
               
                 N883G 
                 0.42 
                 0.08 
                 0.37 
                 0.08 
                 0.03 
                 0.11 
                 Yes 
                 Yes 
               
               
                 N883K 
                 0.12 
                 0.16 
                 0.23 
                 0.16 
                 0.16 
                 0.10 
                 Yes 
                 Yes 
               
               
                 N883A 
                 −0.26 
                 0.15 
                 −1.10 
                 0.17 
                 0.05 
                 0.55 
                 Yes 
                 No 
               
               
                 N883R 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.84 
                 0.11 
                 Yes 
                 No 
               
               
                 N883D 
                 −0.02 
                 0.13 
                 −0.37 
                 0.14 
                 −0.36 
                 0.18 
                 No 
                 No 
               
               
                 N883I 
                 0.00 
                 0.16 
                 0.08 
                 0.15 
                 −0.37 
                 0.12 
                 Yes 
                 No 
               
               
                 N883S 
                 0.08 
                 0.10 
                 0.04 
                 0.10 
                 −0.13 
                 0.09 
                 Yes 
                 No 
               
               
                 N883T 
                 0.27 
                 0.11 
                 −0.02 
                 0.11 
                 −0.21 
                 0.12 
                 Yes 
                 No 
               
               
                 S884V 
                 0.05 
                 0.11 
                 0.61 
                 0.10 
                 0.03 
                 0.14 
                 Yes 
                 Yes 
               
               
                 S884A 
                 0.07 
                 0.13 
                 −0.01 
                 0.12 
                 0.02 
                 NA 
                 Yes 
                 No 
               
               
                 S884R 
                 −0.28 
                 0.06 
                 −0.11 
                 0.06 
                 0.34 
                 0.07 
                 Yes 
                 No 
               
               
                 S884N 
                 0.14 
                 0.14 
                 0.48 
                 0.13 
                 −0.07 
                 0.25 
                 Yes 
                 No 
               
               
                 S884C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.18 
                 0.19 
                 Yes 
                 No 
               
               
                 S884E 
                 −0.10 
                 0.16 
                 −0.04 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S884G 
                 −0.09 
                 0.06 
                 −0.11 
                 0.06 
                 0.01 
                 0.10 
                 Yes 
                 No 
               
               
                 S884L 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.02 
                 0.55 
                 Yes 
                 No 
               
               
                 S884T 
                 −0.01 
                 0.10 
                 0.05 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S884W 
                 −0.99 
                 0.18 
                 −0.38 
                 0.14 
                 0.43 
                 0.82 
                 Yes 
                 No 
               
               
                 P885A 
                 −0.36 
                 0.06 
                 −0.32 
                 0.05 
                 −0.12 
                 0.13 
                 No 
                 No 
               
               
                 P885R 
                 −0.03 
                 0.04 
                 −0.89 
                 0.05 
                 0.00 
                 0.06 
                 Yes 
                 No 
               
               
                 P885N 
                 −0.47 
                 0.17 
                 −0.73 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P885D 
                 −0.73 
                 0.12 
                 −1.21 
                 0.12 
                 −0.83 
                 0.35 
                 No 
                 No 
               
               
                 P885C 
                 −1.54 
                 0.14 
                 −0.39 
                 0.09 
                 −0.01 
                 0.09 
                 No 
                 No 
               
               
                 P885Q 
                 −1.26 
                 0.18 
                 −0.04 
                 0.13 
                 −0.65 
                 0.33 
                 No 
                 No 
               
               
                 P885E 
                 −0.08 
                 0.08 
                 −1.01 
                 0.09 
                 −0.98 
                 0.16 
                 No 
                 No 
               
               
                 P885G 
                 −1.22 
                 0.05 
                 −0.98 
                 0.04 
                 −0.39 
                 0.04 
                 No 
                 No 
               
               
                 P885H 
                 −0.06 
                 0.13 
                 −0.41 
                 0.13 
                 0.09 
                 0.12 
                 Yes 
                 No 
               
               
                 P885I 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.01 
                 0.44 
                 Yes 
                 No 
               
               
                 P885L 
                 −0.66 
                 0.07 
                 −0.90 
                 0.07 
                 −0.60 
                 0.05 
                 No 
                 No 
               
               
                 P885K 
                 −0.12 
                 0.12 
                 −0.28 
                 0.12 
                 −0.32 
                 0.22 
                 No 
                 No 
               
               
                 P885M 
                 −1.32 
                 0.15 
                 −1.01 
                 0.13 
                 −0.52 
                 0.13 
                 No 
                 No 
               
               
                 P885F 
                 −0.98 
                 0.16 
                 −0.49 
                 0.14 
                 −0.31 
                 0.10 
                 No 
                 No 
               
               
                 P885S 
                 −0.88 
                 0.07 
                 −0.65 
                 0.06 
                 −0.11 
                 0.12 
                 No 
                 No 
               
               
                 P885T 
                 −0.35 
                 0.04 
                 −0.29 
                 0.04 
                 0.03 
                 0.05 
                 Yes 
                 No 
               
               
                 P885W 
                 −0.76 
                 0.07 
                 −1.20 
                 0.08 
                 −0.94 
                 0.23 
                 No 
                 No 
               
               
                 P885Y 
                 −0.19 
                 0.16 
                 0.72 
                 0.13 
                 0.22 
                 0.48 
                 Yes 
                 No 
               
               
                 P885V 
                 −0.86 
                 0.06 
                 −0.46 
                 0.05 
                 0.05 
                 0.12 
                 Yes 
                 No 
               
               
                 S886L 
                 0.09 
                 0.08 
                 0.12 
                 0.08 
                 0.05 
                 0.11 
                 Yes 
                 Yes 
               
               
                 S886M 
                 0.32 
                 0.11 
                 0.15 
                 0.11 
                 0.40 
                 0.35 
                 Yes 
                 Yes 
               
               
                 S886W 
                 0.23 
                 0.07 
                 0.01 
                 0.07 
                 0.70 
                 0.19 
                 Yes 
                 Yes 
               
               
                 S886A 
                 −0.52 
                 0.07 
                 −0.42 
                 0.07 
                 −0.04 
                 0.14 
                 No 
                 No 
               
               
                 S886R 
                 0.12 
                 0.04 
                 −0.08 
                 0.04 
                 0.36 
                 0.04 
                 Yes 
                 No 
               
               
                 S886N 
                 0.34 
                 0.10 
                 −0.34 
                 0.11 
                 −0.03 
                 0.14 
                 Yes 
                 No 
               
               
                 S886D 
                 0.60 
                 0.10 
                 −0.69 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S886C 
                 0.11 
                 0.09 
                 −0.64 
                 0.09 
                 0.34 
                 0.23 
                 Yes 
                 No 
               
               
                 S886Q 
                 −0.33 
                 0.14 
                 −0.65 
                 0.14 
                 0.19 
                 0.64 
                 Yes 
                 No 
               
               
                 S886E 
                 −0.60 
                 0.10 
                 −0.56 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 S886G 
                 −0.20 
                 0.04 
                 −0.18 
                 0.04 
                 0.10 
                 0.05 
                 Yes 
                 No 
               
               
                 S886I 
                 0.89 
                 0.13 
                 −0.13 
                 0.14 
                 0.07 
                 0.29 
                 Yes 
                 No 
               
               
                 S886K 
                 −0.70 
                 0.14 
                 0.01 
                 0.12 
                 0.56 
                 0.12 
                 Yes 
                 No 
               
               
                 S886F 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.75 
                 0.44 
                 Yes 
                 No 
               
               
                 S886P 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.28 
                 0.14 
                 Yes 
                 No 
               
               
                 S886T 
                 0.07 
                 0.07 
                 −0.05 
                 0.07 
                 −0.29 
                 0.10 
                 Yes 
                 No 
               
               
                 S886Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.79 
                 0.55 
                 Yes 
                 No 
               
               
                 S886V 
                 −0.10 
                 0.07 
                 −0.15 
                 0.06 
                 0.35 
                 0.20 
                 Yes 
                 No 
               
               
                 K887A 
                 0.03 
                 0.04 
                 −0.38 
                 0.05 
                 −0.54 
                 0.04 
                 Yes 
                 No 
               
               
                 K887R 
                 −0.09 
                 0.03 
                 −0.04 
                 0.03 
                 0.21 
                 0.03 
                 Yes 
                 No 
               
               
                 K887N 
                 0.24 
                 0.10 
                 0.07 
                 0.10 
                 −0.45 
                 0.24 
                 Yes 
                 No 
               
               
                 K887D 
                 −1.19 
                 0.10 
                 −0.97 
                 0.09 
                 −1.27 
                 0.28 
                 No 
                 No 
               
               
                 K887C 
                 −0.76 
                 0.08 
                 0.16 
                 0.07 
                 −0.59 
                 0.06 
                 Yes 
                 No 
               
               
                 K887Q 
                 0.10 
                 0.08 
                 −0.05 
                 0.07 
                 −0.25 
                 0.11 
                 Yes 
                 No 
               
               
                 K887E 
                 −0.33 
                 0.05 
                 −0.39 
                 0.05 
                 −0.97 
                 0.06 
                 No 
                 No 
               
               
                 K887G 
                 −0.14 
                 0.03 
                 −0.22 
                 0.02 
                 −0.42 
                 0.03 
                 No 
                 No 
               
               
                 K887H 
                 −0.04 
                 0.12 
                 −1.21 
                 0.15 
                 −0.21 
                 0.40 
                 No 
                 No 
               
               
                 K887I 
                 −0.31 
                 0.12 
                 −0.04 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K887L 
                 −0.88 
                 0.06 
                 −0.67 
                 0.05 
                 −0.68 
                 0.07 
                 No 
                 No 
               
               
                 K887M 
                 −0.12 
                 0.07 
                 −0.23 
                 0.07 
                 −0.44 
                 0.16 
                 No 
                 No 
               
               
                 K887F 
                 0.22 
                 0.11 
                 −0.22 
                 0.11 
                 −0.74 
                 0.25 
                 Yes 
                 No 
               
               
                 K887P 
                 −0.29 
                 0.08 
                 −0.61 
                 0.08 
                 −0.32 
                 0.18 
                 No 
                 No 
               
               
                 K887S 
                 −0.03 
                 0.05 
                 −0.50 
                 0.05 
                 −0.66 
                 0.08 
                 No 
                 No 
               
               
                 K887* 
                 −0.88 
                 0.08 
                 −1.30 
                 0.08 
                 −1.22 
                 0.10 
                 No 
                 No 
               
               
                 K887T 
                 −0.79 
                 0.08 
                 −0.22 
                 0.07 
                 −0.74 
                 0.11 
                 No 
                 No 
               
               
                 K887W 
                 −0.59 
                 0.05 
                 −0.69 
                 0.05 
                 −0.65 
                 0.07 
                 No 
                 No 
               
               
                 K887Y 
                 0.36 
                 0.10 
                 −0.98 
                 0.13 
                 −0.40 
                 0.17 
                 Yes 
                 No 
               
               
                 K887V 
                 0.09 
                 0.04 
                 −0.88 
                 0.04 
                 −0.89 
                 0.07 
                 Yes 
                 No 
               
               
                 F888A 
                 −2.01 
                 0.10 
                 −1.31 
                 0.07 
                 −1.30 
                 0.28 
                 No 
                 No 
               
               
                 F888R 
                 −1.27 
                 0.07 
                 −1.04 
                 0.06 
                 −1.82 
                 0.18 
                 No 
                 No 
               
               
                 F888D 
                 −1.09 
                 0.12 
                 −1.32 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F888C 
                 0.01 
                 0.04 
                 −0.10 
                 0.04 
                 0.10 
                 0.03 
                 Yes 
                 No 
               
               
                 F888Q 
                 −0.58 
                 0.13 
                 −1.37 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F888E 
                 −0.89 
                 0.08 
                 −2.09 
                 0.11 
                 −1.77 
                 0.12 
                 No 
                 No 
               
               
                 F888G 
                 −1.75 
                 0.05 
                 −1.53 
                 0.05 
                 −1.57 
                 0.03 
                 No 
                 No 
               
               
                 F888I 
                 0.09 
                 0.11 
                 −0.24 
                 0.11 
                 −0.50 
                 0.15 
                 Yes 
                 No 
               
               
                 F888L 
                 −0.13 
                 0.04 
                 −0.06 
                 0.03 
                 −0.23 
                 0.05 
                 No 
                 No 
               
               
                 F888M 
                 −0.65 
                 0.12 
                 0.31 
                 0.10 
                 −0.04 
                 0.10 
                 Yes 
                 No 
               
               
                 F888P 
                 −0.69 
                 0.12 
                 −1.56 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 F888S 
                 −1.42 
                 0.08 
                 −1.17 
                 0.07 
                 −1.14 
                 0.12 
                 No 
                 No 
               
               
                 F888* 
                 −1.06 
                 0.13 
                 −0.77 
                 0.11 
                 −1.31 
                 0.08 
                 No 
                 No 
               
               
                 F888T 
                 −0.62 
                 0.11 
                 −1.69 
                 0.13 
                 −1.19 
                 0.64 
                 No 
                 No 
               
               
                 F888W 
                 −1.15 
                 0.08 
                 −2.14 
                 0.11 
                 −1.37 
                 0.05 
                 No 
                 No 
               
               
                 F888Y 
                 −0.73 
                 0.13 
                 −1.27 
                 0.14 
                 −0.60 
                 0.12 
                 No 
                 No 
               
               
                 F888V 
                 0.07 
                 0.04 
                 0.10 
                 0.04 
                 −0.31 
                 0.03 
                 Yes 
                 No 
               
               
                 N889A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.86 
                 0.64 
                 Yes 
                 No 
               
               
                 N889R 
                 −0.94 
                 0.09 
                 −0.07 
                 0.07 
                 −0.55 
                 0.48 
                 No 
                 No 
               
               
                 N889D 
                 −0.34 
                 0.10 
                 −0.44 
                 0.10 
                 −0.39 
                 0.14 
                 No 
                 No 
               
               
                 N889G 
                 −0.87 
                 0.06 
                 −1.32 
                 0.07 
                 −0.83 
                 0.07 
                 No 
                 No 
               
               
                 N889I 
                 −0.51 
                 0.17 
                 −0.43 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N889K 
                 −0.76 
                 0.17 
                 −0.47 
                 0.15 
                 −0.34 
                 0.24 
                 No 
                 No 
               
               
                 N889S 
                 −1.13 
                 0.11 
                 0.08 
                 0.08 
                 −0.26 
                 0.14 
                 Yes 
                 No 
               
               
                 N889T 
                 −0.55 
                 0.16 
                 −0.45 
                 0.14 
                 −0.36 
                 0.30 
                 No 
                 No 
               
               
                 N889V 
                 −1.82 
                 0.15 
                 −1.28 
                 0.12 
                 −1.16 
                 0.64 
                 No 
                 No 
               
               
                 Q890C 
                 0.03 
                 0.11 
                 0.64 
                 0.10 
                 0.08 
                 0.54 
                 Yes 
                 Yes 
               
               
                 Q890H 
                 0.39 
                 0.09 
                 0.07 
                 0.09 
                 0.04 
                 0.11 
                 Yes 
                 Yes 
               
               
                 Q890W 
                 0.03 
                 0.08 
                 0.23 
                 0.07 
                 0.03 
                 0.08 
                 Yes 
                 Yes 
               
               
                 Q890A 
                 0.39 
                 0.06 
                 0.05 
                 0.06 
                 −0.02 
                 0.11 
                 Yes 
                 No 
               
               
                 Q890R 
                 −0.10 
                 0.05 
                 −0.24 
                 0.05 
                 −0.05 
                 0.10 
                 No 
                 No 
               
               
                 Q890N 
                 −0.25 
                 0.15 
                 −0.66 
                 0.16 
                 0.31 
                 NA 
                 Yes 
                 No 
               
               
                 Q890D 
                 0.54 
                 0.10 
                 −0.52 
                 0.11 
                 −0.35 
                 0.20 
                 Yes 
                 No 
               
               
                 Q890E 
                 0.17 
                 0.06 
                 −0.62 
                 0.07 
                 −0.33 
                 0.06 
                 Yes 
                 No 
               
               
                 Q890G 
                 −0.35 
                 0.04 
                 −0.60 
                 0.04 
                 −0.15 
                 0.07 
                 No 
                 No 
               
               
                 Q890I 
                 −0.26 
                 0.16 
                 −0.94 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 Q890L 
                 0.09 
                 0.06 
                 −0.14 
                 0.06 
                 0.29 
                 0.17 
                 Yes 
                 No 
               
               
                 Q890K 
                 0.23 
                 0.10 
                 0.25 
                 0.10 
                 −0.22 
                 0.16 
                 Yes 
                 No 
               
               
                 Q890M 
                 0.32 
                 0.11 
                 −0.13 
                 0.11 
                 −0.07 
                 0.48 
                 Yes 
                 No 
               
               
                 Q890F 
                 0.25 
                 0.15 
                 −0.11 
                 0.15 
                 0.09 
                 0.82 
                 Yes 
                 No 
               
               
                 Q890P 
                 −1.20 
                 0.12 
                 −0.75 
                 0.10 
                 −0.11 
                 0.17 
                 No 
                 No 
               
               
                 Q890S 
                 −0.58 
                 0.08 
                 −0.01 
                 0.07 
                 −0.19 
                 0.08 
                 No 
                 No 
               
               
                 Q890* 
                 −1.12 
                 0.11 
                 −1.26 
                 0.11 
                 −0.88 
                 0.13 
                 No 
                 No 
               
               
                 Q890T 
                 −0.36 
                 0.10 
                 0.11 
                 0.09 
                 0.08 
                 0.09 
                 Yes 
                 No 
               
               
                 Q890Y 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.03 
                 0.13 
                 Yes 
                 No 
               
               
                 Q890V 
                 −0.39 
                 0.06 
                 −0.33 
                 0.06 
                 0.21 
                 0.06 
                 Yes 
                 No 
               
               
                 R891A 
                 −0.41 
                 0.08 
                 −0.46 
                 0.07 
                 −0.44 
                 0.31 
                 No 
                 No 
               
               
                 R891D 
                 −1.17 
                 0.16 
                 −0.76 
                 0.14 
                 −0.63 
                 0.64 
                 No 
                 No 
               
               
                 R891C 
                 −0.10 
                 0.10 
                 −0.56 
                 0.11 
                 −0.05 
                 0.17 
                 No 
                 No 
               
               
                 R891Q 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.08 
                 0.64 
                 Yes 
                 No 
               
               
                 R891E 
                 −1.06 
                 0.11 
                 −0.65 
                 0.09 
                 −0.59 
                 0.64 
                 No 
                 No 
               
               
                 R891G 
                 −0.70 
                 0.04 
                 −0.40 
                 0.04 
                 −0.11 
                 0.04 
                 No 
                 No 
               
               
                 R891L 
                 0.07 
                 0.08 
                 −0.02 
                 0.08 
                 −0.25 
                 0.33 
                 Yes 
                 No 
               
               
                 R891K 
                 −0.04 
                 0.11 
                 −0.37 
                 0.11 
                 −0.03 
                 0.26 
                 No 
                 No 
               
               
                 R891M 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.14 
                 NA 
                 Yes 
                 No 
               
               
                 R891S 
                 −0.18 
                 0.07 
                 −0.49 
                 0.07 
                 −0.28 
                 0.08 
                 No 
                 No 
               
               
                 R891* 
                 −0.88 
                 0.13 
                 −0.57 
                 0.11 
                 −0.74 
                 0.20 
                 No 
                 No 
               
               
                 R891T 
                 −0.20 
                 0.10 
                 −0.28 
                 0.10 
                 −0.16 
                 0.10 
                 No 
                 No 
               
               
                 R891W 
                 −1.03 
                 0.08 
                 −1.42 
                 0.08 
                 −0.78 
                 0.43 
                 No 
                 No 
               
               
                 R891V 
                 −0.28 
                 0.07 
                 −0.77 
                 0.07 
                 −0.53 
                 0.09 
                 No 
                 No 
               
               
                 V892A 
                 −1.02 
                 0.08 
                 −1.08 
                 0.08 
                 −0.18 
                 0.07 
                 No 
                 No 
               
               
                 V892R 
                 −1.49 
                 0.09 
                 −1.55 
                 0.08 
                 −1.41 
                 0.09 
                 No 
                 No 
               
               
                 V892C 
                 −0.58 
                 0.14 
                 −0.80 
                 0.14 
                 −0.01 
                 0.13 
                 No 
                 No 
               
               
                 V892E 
                 −0.97 
                 0.10 
                 −1.28 
                 0.10 
                 −0.93 
                 0.17 
                 No 
                 No 
               
               
                 V892G 
                 −1.01 
                 0.05 
                 −1.11 
                 0.05 
                 −0.90 
                 0.05 
                 No 
                 No 
               
               
                 V892L 
                 −0.58 
                 0.09 
                 −1.35 
                 0.10 
                 −0.93 
                 0.14 
                 No 
                 No 
               
               
                 V892M 
                 −0.59 
                 0.12 
                 −0.62 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V892S 
                 −1.15 
                 0.13 
                 −1.21 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 V892T 
                 −0.34 
                 0.15 
                 0.05 
                 0.13 
                 0.11 
                 0.64 
                 Yes 
                 No 
               
               
                 V892W 
                 −1.99 
                 0.15 
                 −1.09 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N893A 
                 −1.02 
                 0.07 
                 −0.18 
                 0.05 
                 −0.37 
                 0.05 
                 No 
                 No 
               
               
                 N893R 
                 −0.35 
                 0.04 
                 −0.57 
                 0.04 
                 −0.42 
                 0.06 
                 No 
                 No 
               
               
                 N893D 
                 −0.71 
                 0.10 
                 −0.39 
                 0.08 
                 −0.71 
                 0.11 
                 No 
                 No 
               
               
                 N893C 
                 −0.80 
                 0.10 
                 −0.20 
                 0.09 
                 −0.24 
                 0.07 
                 No 
                 No 
               
               
                 N893Q 
                 −1.58 
                 0.15 
                 −0.86 
                 0.11 
                 −0.57 
                 0.20 
                 No 
                 No 
               
               
                 N893E 
                 −0.89 
                 0.07 
                 −1.03 
                 0.07 
                 −1.10 
                 0.10 
                 No 
                 No 
               
               
                 N893G 
                 −0.30 
                 0.03 
                 −0.68 
                 0.03 
                 −0.34 
                 0.04 
                 No 
                 No 
               
               
                 N893H 
                 0.02 
                 0.13 
                 −0.74 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N893I 
                 0.33 
                 0.11 
                 −0.24 
                 0.12 
                 −0.68 
                 0.11 
                 Yes 
                 No 
               
               
                 N893L 
                 −1.03 
                 0.08 
                 −0.46 
                 0.07 
                 −0.86 
                 0.17 
                 No 
                 No 
               
               
                 N893K 
                 −0.39 
                 0.07 
                 −0.07 
                 0.06 
                 −0.27 
                 0.07 
                 No 
                 No 
               
               
                 N893M 
                 0.26 
                 0.08 
                 −0.81 
                 0.10 
                 −1.04 
                 0.33 
                 Yes 
                 No 
               
               
                 N893S 
                 0.64 
                 0.05 
                 0.08 
                 0.05 
                 −0.47 
                 0.06 
                 Yes 
                 No 
               
               
                 N893* 
                 −1.54 
                 0.12 
                 −1.43 
                 0.11 
                 −1.26 
                 0.17 
                 No 
                 No 
               
               
                 N893T 
                 1.09 
                 0.06 
                 −0.04 
                 0.06 
                 −0.62 
                 0.08 
                 Yes 
                 No 
               
               
                 N893W 
                 −0.63 
                 0.06 
                 −0.48 
                 0.06 
                 −0.78 
                 0.10 
                 No 
                 No 
               
               
                 N893Y 
                 −0.51 
                 0.12 
                 −0.87 
                 0.12 
                 −0.38 
                 0.18 
                 No 
                 No 
               
               
                 N893V 
                 −0.70 
                 0.06 
                 −0.74 
                 0.06 
                 −0.59 
                 0.05 
                 No 
                 No 
               
               
                 A894R 
                 0.19 
                 0.06 
                 0.06 
                 0.06 
                 0.04 
                 0.08 
                 Yes 
                 Yes 
               
               
                 A894D 
                 0.04 
                 0.06 
                 0.09 
                 0.06 
                 0.21 
                 0.05 
                 Yes 
                 Yes 
               
               
                 A894C 
                 −0.13 
                 0.15 
                 −0.29 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A894Q 
                 0.87 
                 0.14 
                 −0.47 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A894E 
                 −0.35 
                 0.10 
                 −0.85 
                 0.10 
                 −0.45 
                 0.20 
                 No 
                 No 
               
               
                 A894G 
                 −0.47 
                 0.05 
                 0.09 
                 0.05 
                 0.21 
                 0.06 
                 Yes 
                 No 
               
               
                 A894L 
                 −0.45 
                 0.11 
                 0.57 
                 0.09 
                 0.08 
                 0.12 
                 Yes 
                 No 
               
               
                 A894K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.27 
                 0.15 
                 Yes 
                 No 
               
               
                 A894M 
                 0.14 
                 0.13 
                 −0.17 
                 0.13 
                 0.25 
                 0.18 
                 Yes 
                 No 
               
               
                 A894P 
                 −0.67 
                 0.14 
                 −1.05 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A894S 
                 0.57 
                 0.08 
                 −0.97 
                 0.10 
                 0.12 
                 0.23 
                 Yes 
                 No 
               
               
                 A894* 
                 −0.76 
                 0.19 
                 0.06 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 A894T 
                 −0.68 
                 0.10 
                 −0.49 
                 0.09 
                 0.21 
                 0.15 
                 Yes 
                 No 
               
               
                 A894W 
                 0.67 
                 0.09 
                 −0.44 
                 0.10 
                 0.02 
                 0.54 
                 Yes 
                 No 
               
               
                 A894V 
                 −0.22 
                 0.07 
                 −0.05 
                 0.06 
                 0.12 
                 0.18 
                 Yes 
                 No 
               
               
                 Y895D 
                 0.16 
                 0.04 
                 0.00 
                 0.04 
                 0.09 
                 0.04 
                 Yes 
                 Yes 
               
               
                 Y895A 
                 −1.08 
                 0.12 
                 −0.85 
                 0.11 
                 −0.53 
                 0.37 
                 No 
                 No 
               
               
                 Y895R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.75 
                 0.07 
                 Yes 
                 No 
               
               
                 Y895N 
                 −0.12 
                 0.11 
                 −0.43 
                 0.11 
                 −0.07 
                 0.23 
                 No 
                 No 
               
               
                 Y895C 
                 0.61 
                 0.06 
                 0.14 
                 0.06 
                 −0.26 
                 0.07 
                 Yes 
                 No 
               
               
                 Y895E 
                 −0.53 
                 0.11 
                 −0.74 
                 0.10 
                 −0.62 
                 0.13 
                 No 
                 No 
               
               
                 Y895G 
                 −0.59 
                 0.06 
                 −1.69 
                 0.08 
                 −1.72 
                 0.07 
                 No 
                 No 
               
               
                 Y895H 
                 −0.21 
                 0.10 
                 −0.10 
                 0.10 
                 −0.25 
                 0.16 
                 No 
                 No 
               
               
                 Y895F 
                 0.70 
                 0.12 
                 −0.28 
                 0.13 
                 −0.20 
                 0.21 
                 Yes 
                 No 
               
               
                 Y895S 
                 0.18 
                 0.05 
                 −0.17 
                 0.05 
                 −0.12 
                 0.06 
                 Yes 
                 No 
               
               
                 Y895* 
                 −0.03 
                 0.05 
                 −0.04 
                 0.05 
                 0.16 
                 0.06 
                 Yes 
                 No 
               
               
                 Y895W 
                 −0.08 
                 0.11 
                 0.17 
                 0.10 
                 −0.18 
                 0.31 
                 Yes 
                 No 
               
               
                 Y895V 
                 −1.60 
                 0.12 
                 −0.11 
                 0.08 
                 −0.61 
                 0.40 
                 No 
                 No 
               
               
                 L896A 
                 −1.48 
                 0.09 
                 −1.26 
                 0.08 
                 −1.68 
                 0.35 
                 No 
                 No 
               
               
                 L896R 
                 0.19 
                 0.04 
                 −0.11 
                 0.04 
                 −0.30 
                 0.04 
                 Yes 
                 No 
               
               
                 L896Q 
                 0.42 
                 0.04 
                 0.08 
                 0.04 
                 −0.17 
                 0.05 
                 Yes 
                 No 
               
               
                 L896E 
                 −1.31 
                 0.11 
                 −1.65 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L896G 
                 −2.17 
                 0.07 
                 −1.66 
                 0.05 
                 −1.77 
                 0.05 
                 No 
                 No 
               
               
                 L896M 
                 0.31 
                 0.11 
                 −0.22 
                 0.11 
                 −0.74 
                 0.17 
                 Yes 
                 No 
               
               
                 L896F 
                 −0.69 
                 0.18 
                 −0.97 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 L896P 
                 −0.37 
                 0.08 
                 −0.52 
                 0.08 
                 −0.53 
                 0.10 
                 No 
                 No 
               
               
                 L896S 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.38 
                 0.48 
                 Yes 
                 No 
               
               
                 L896W 
                 −1.69 
                 0.12 
                 −1.64 
                 0.11 
                 −0.97 
                 0.54 
                 No 
                 No 
               
               
                 L896V 
                 −0.04 
                 0.06 
                 −0.69 
                 0.06 
                 −0.81 
                 0.07 
                 No 
                 No 
               
               
                 K897A 
                 −0.76 
                 0.08 
                 −0.22 
                 0.07 
                 −0.07 
                 0.15 
                 No 
                 No 
               
               
                 K897R 
                 0.03 
                 0.04 
                 −0.01 
                 0.04 
                 −0.05 
                 0.05 
                 Yes 
                 No 
               
               
                 K897N 
                 0.58 
                 0.11 
                 0.26 
                 0.11 
                 −0.06 
                 0.09 
                 Yes 
                 No 
               
               
                 K897D 
                 −1.39 
                 0.13 
                 −0.61 
                 0.10 
                 −0.10 
                 0.25 
                 No 
                 No 
               
               
                 K897C 
                 0.02 
                 0.09 
                 −0.54 
                 0.10 
                 −0.11 
                 0.08 
                 Yes 
                 No 
               
               
                 K897Q 
                 −0.06 
                 0.10 
                 0.16 
                 0.10 
                 −0.04 
                 0.21 
                 Yes 
                 No 
               
               
                 K897E 
                 0.17 
                 0.05 
                 −0.03 
                 0.05 
                 −0.29 
                 0.08 
                 Yes 
                 No 
               
               
                 K897G 
                 0.01 
                 0.04 
                 −0.29 
                 0.04 
                 −0.07 
                 0.03 
                 Yes 
                 No 
               
               
                 K897H 
                 −0.18 
                 0.15 
                 0.06 
                 0.14 
                 0.22 
                 0.36 
                 Yes 
                 No 
               
               
                 K897I 
                 −0.29 
                 0.13 
                 −1.02 
                 0.14 
                 −0.06 
                 0.06 
                 No 
                 No 
               
               
                 K897L 
                 −0.19 
                 0.07 
                 −0.26 
                 0.07 
                 0.28 
                 0.35 
                 Yes 
                 No 
               
               
                 K897M 
                 −0.35 
                 0.09 
                 −0.01 
                 0.08 
                 0.23 
                 0.11 
                 Yes 
                 No 
               
               
                 K897F 
                 −0.72 
                 0.18 
                 0.16 
                 0.15 
                 −0.08 
                 0.64 
                 Yes 
                 No 
               
               
                 K897P 
                 −1.22 
                 0.13 
                 −1.78 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 K897S 
                 −0.22 
                 0.07 
                 −0.29 
                 0.07 
                 −0.13 
                 0.10 
                 No 
                 No 
               
               
                 K897* 
                 −0.92 
                 0.11 
                 −0.93 
                 0.11 
                 −0.93 
                 0.11 
                 No 
                 No 
               
               
                 K897T 
                 0.27 
                 0.08 
                 −0.32 
                 0.08 
                 −0.02 
                 0.06 
                 Yes 
                 No 
               
               
                 K897W 
                 −0.08 
                 0.07 
                 −0.54 
                 0.07 
                 0.00 
                 0.19 
                 No 
                 No 
               
               
                 K897Y 
                 −0.95 
                 0.19 
                 0.19 
                 0.14 
                 −0.23 
                 0.13 
                 Yes 
                 No 
               
               
                 K897V 
                 −0.30 
                 0.05 
                 −0.29 
                 0.05 
                 0.19 
                 0.07 
                 Yes 
                 No 
               
               
                 E898A 
                 −0.19 
                 0.06 
                 0.08 
                 0.06 
                 −0.25 
                 0.07 
                 Yes 
                 No 
               
               
                 E898R 
                 −0.44 
                 0.07 
                 −0.49 
                 0.07 
                 −0.10 
                 0.31 
                 No 
                 No 
               
               
                 E898D 
                 0.42 
                 0.10 
                 −0.32 
                 0.11 
                 −0.12 
                 0.16 
                 Yes 
                 No 
               
               
                 E898C 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.23 
                 0.15 
                 Yes 
                 No 
               
               
                 E898Q 
                 −0.43 
                 0.14 
                 −0.57 
                 0.13 
                 0.29 
                 0.39 
                 Yes 
                 No 
               
               
                 E898G 
                 −0.27 
                 0.05 
                 −0.27 
                 0.05 
                 0.12 
                 0.06 
                 Yes 
                 No 
               
               
                 E898L 
                 0.07 
                 0.11 
                 −0.46 
                 0.12 
                 0.15 
                 0.12 
                 Yes 
                 No 
               
               
                 E898K 
                 −0.93 
                 0.16 
                 −0.35 
                 0.14 
                 0.13 
                 0.31 
                 Yes 
                 No 
               
               
                 E898P 
                 −0.40 
                 0.19 
                 −0.60 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E898S 
                 0.17 
                 0.14 
                 −1.32 
                 0.18 
                 0.38 
                 0.55 
                 Yes 
                 No 
               
               
                 E898W 
                 −1.01 
                 0.12 
                 −1.33 
                 0.12 
                 −0.16 
                 0.14 
                 No 
                 No 
               
               
                 E898V 
                 −0.06 
                 0.07 
                 0.31 
                 0.07 
                 0.01 
                 0.07 
                 Yes 
                 No 
               
               
                 H899A 
                 0.21 
                 0.08 
                 0.16 
                 0.07 
                 0.01 
                 0.48 
                 Yes 
                 Yes 
               
               
                 H899N 
                 0.15 
                 0.15 
                 0.70 
                 0.14 
                 0.08 
                 0.18 
                 Yes 
                 Yes 
               
               
                 H899R 
                 −0.20 
                 0.04 
                 −0.12 
                 0.04 
                 −0.12 
                 0.03 
                 No 
                 No 
               
               
                 H899D 
                 −0.84 
                 0.13 
                 −0.16 
                 0.11 
                 −0.47 
                 0.25 
                 No 
                 No 
               
               
                 H899C 
                 −0.98 
                 0.14 
                 −0.02 
                 0.11 
                 −0.12 
                 0.13 
                 No 
                 No 
               
               
                 H899Q 
                 −0.15 
                 0.05 
                 −0.20 
                 0.05 
                 0.00 
                 0.03 
                 No 
                 No 
               
               
                 H899E 
                 −0.85 
                 0.10 
                 −0.64 
                 0.09 
                 −0.36 
                 0.27 
                 No 
                 No 
               
               
                 H899G 
                 −0.79 
                 0.05 
                 −0.96 
                 0.05 
                 −0.65 
                 0.05 
                 No 
                 No 
               
               
                 H899L 
                 −0.27 
                 0.08 
                 −0.41 
                 0.08 
                 −0.50 
                 0.14 
                 No 
                 No 
               
               
                 H899K 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.05 
                 0.49 
                 Yes 
                 No 
               
               
                 H899P 
                 −0.07 
                 0.07 
                 0.01 
                 0.07 
                 −0.33 
                 0.10 
                 Yes 
                 No 
               
               
                 H899S 
                 −0.31 
                 0.10 
                 −0.33 
                 0.09 
                 0.07 
                 0.32 
                 Yes 
                 No 
               
               
                 H899T 
                 −0.37 
                 0.15 
                 −0.14 
                 0.14 
                 −0.03 
                 0.48 
                 No 
                 No 
               
               
                 H899W 
                 −0.32 
                 0.08 
                 −0.24 
                 0.07 
                 −0.25 
                 0.48 
                 No 
                 No 
               
               
                 H899Y 
                 −0.09 
                 0.12 
                 −0.87 
                 0.13 
                 0.11 
                 0.16 
                 Yes 
                 No 
               
               
                 H899V 
                 −0.07 
                 0.07 
                 −0.99 
                 0.08 
                 0.05 
                 0.22 
                 Yes 
                 No 
               
               
                 P900A 
                 −0.09 
                 0.05 
                 0.03 
                 0.04 
                 0.04 
                 0.11 
                 Yes 
                 No 
               
               
                 P900R 
                 −0.17 
                 0.04 
                 −0.23 
                 0.03 
                 0.09 
                 0.04 
                 Yes 
                 No 
               
               
                 P900N 
                 −1.13 
                 0.14 
                 0.05 
                 0.11 
                 0.35 
                 0.30 
                 Yes 
                 No 
               
               
                 P900D 
                 −0.42 
                 0.08 
                 −0.19 
                 0.07 
                 0.19 
                 0.12 
                 Yes 
                 No 
               
               
                 P900C 
                 −0.28 
                 0.07 
                 0.15 
                 0.06 
                 0.12 
                 0.15 
                 Yes 
                 No 
               
               
                 P900Q 
                 0.28 
                 0.08 
                 −0.19 
                 0.09 
                 0.23 
                 0.30 
                 Yes 
                 No 
               
               
                 P900E 
                 −0.19 
                 0.06 
                 0.18 
                 0.05 
                 0.29 
                 0.08 
                 Yes 
                 No 
               
               
                 P900G 
                 −0.03 
                 0.03 
                 −0.15 
                 0.03 
                 0.11 
                 0.03 
                 Yes 
                 No 
               
               
                 P900H 
                 0.07 
                 0.08 
                 −0.18 
                 0.08 
                 0.25 
                 0.12 
                 Yes 
                 No 
               
               
                 P900I 
                 −0.83 
                 0.12 
                 −0.36 
                 0.10 
                 0.33 
                 0.33 
                 Yes 
                 No 
               
               
                 P900L 
                 0.03 
                 0.04 
                 −0.20 
                 0.04 
                 0.07 
                 0.04 
                 Yes 
                 No 
               
               
                 P900K 
                 0.16 
                 0.08 
                 −0.61 
                 0.08 
                 0.05 
                 0.13 
                 Yes 
                 No 
               
               
                 P900M 
                 −1.26 
                 0.10 
                 −0.21 
                 0.07 
                 0.06 
                 0.12 
                 Yes 
                 No 
               
               
                 P900F 
                 0.33 
                 0.10 
                 −0.07 
                 0.10 
                 −0.19 
                 0.09 
                 Yes 
                 No 
               
               
                 P900S 
                 −0.10 
                 0.05 
                 0.15 
                 0.04 
                 0.14 
                 0.04 
                 Yes 
                 No 
               
               
                 P900* 
                 −0.32 
                 0.08 
                 −1.30 
                 0.10 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P900T 
                 0.24 
                 0.06 
                 −0.22 
                 0.06 
                 0.19 
                 0.09 
                 Yes 
                 No 
               
               
                 P900W 
                 −0.16 
                 0.05 
                 −0.48 
                 0.06 
                 −0.04 
                 0.06 
                 No 
                 No 
               
               
                 P900Y 
                 −0.49 
                 0.11 
                 −0.86 
                 0.11 
                 −0.25 
                 0.82 
                 No 
                 No 
               
               
                 P900V 
                 0.10 
                 0.04 
                 −0.35 
                 0.04 
                 0.14 
                 0.05 
                 Yes 
                 No 
               
               
                 E901D 
                 0.07 
                 0.10 
                 0.05 
                 0.10 
                 0.14 
                 0.15 
                 Yes 
                 Yes 
               
               
                 E901A 
                 −0.81 
                 0.08 
                 0.24 
                 0.07 
                 0.08 
                 0.08 
                 Yes 
                 No 
               
               
                 E901R 
                 −0.15 
                 0.06 
                 −0.19 
                 0.06 
                 −0.03 
                 0.06 
                 No 
                 No 
               
               
                 E901C 
                 −0.08 
                 0.13 
                 −0.32 
                 0.13 
                 0.21 
                 0.64 
                 Yes 
                 No 
               
               
                 E901Q 
                 −0.69 
                 0.16 
                 0.04 
                 0.13 
                 −0.16 
                 0.40 
                 Yes 
                 No 
               
               
                 E901G 
                 −0.44 
                 0.04 
                 0.07 
                 0.04 
                 0.10 
                 0.06 
                 Yes 
                 No 
               
               
                 E901L 
                 −0.12 
                 0.08 
                 −0.80 
                 0.09 
                 −0.13 
                 0.20 
                 No 
                 No 
               
               
                 E901K 
                 −0.11 
                 0.10 
                 0.20 
                 0.10 
                 0.08 
                 0.13 
                 Yes 
                 No 
               
               
                 E901M 
                 0.16 
                 0.12 
                 −0.14 
                 0.12 
                 0.03 
                 0.82 
                 Yes 
                 No 
               
               
                 E901P 
                 −0.99 
                 0.19 
                 −1.23 
                 0.19 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E901S 
                 −1.40 
                 0.13 
                 0.16 
                 0.08 
                 0.05 
                 0.11 
                 Yes 
                 No 
               
               
                 E901* 
                 −0.29 
                 0.13 
                 −1.11 
                 0.15 
                 −0.63 
                 0.14 
                 No 
                 No 
               
               
                 E901T 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.05 
                 0.44 
                 Yes 
                 No 
               
               
                 E901W 
                 0.02 
                 0.08 
                 −0.49 
                 0.09 
                 0.21 
                 0.08 
                 Yes 
                 No 
               
               
                 E901V 
                 −1.13 
                 0.07 
                 −0.49 
                 0.06 
                 0.11 
                 0.06 
                 Yes 
                 No 
               
               
                 T902A 
                 −0.07 
                 0.05 
                 −0.35 
                 0.05 
                 −0.20 
                 0.09 
                 No 
                 No 
               
               
                 T902R 
                 −0.60 
                 0.06 
                 −1.09 
                 0.07 
                 −0.48 
                 0.12 
                 No 
                 No 
               
               
                 T902C 
                 0.17 
                 0.11 
                 −0.55 
                 0.12 
                 −0.25 
                 0.82 
                 Yes 
                 No 
               
               
                 T902Q 
                 −0.92 
                 0.15 
                 −0.24 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T902E 
                 −0.55 
                 0.10 
                 −1.12 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 T902G 
                 −1.03 
                 0.06 
                 −1.00 
                 0.06 
                 −0.74 
                 0.15 
                 No 
                 No 
               
               
                 T902I 
                 −0.22 
                 0.14 
                 0.19 
                 0.12 
                 −0.10 
                 0.20 
                 Yes 
                 No 
               
               
                 T902L 
                 −0.92 
                 0.11 
                 −0.09 
                 0.09 
                 −0.12 
                 0.09 
                 No 
                 No 
               
               
                 T902K 
                 −0.31 
                 0.04 
                 −0.01 
                 0.04 
                 0.13 
                 0.06 
                 Yes 
                 No 
               
               
                 T902M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.01 
                 0.54 
                 Yes 
                 No 
               
               
                 T902P 
                 −1.06 
                 0.13 
                 −0.32 
                 0.10 
                 −0.81 
                 0.21 
                 No 
                 No 
               
               
                 T902S 
                 −0.15 
                 0.07 
                 −0.38 
                 0.07 
                 −0.15 
                 0.07 
                 No 
                 No 
               
               
                 T902W 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.80 
                 0.54 
                 Yes 
                 No 
               
               
                 T902V 
                 −0.15 
                 0.07 
                 0.06 
                 0.07 
                 −0.03 
                 0.14 
                 Yes 
                 No 
               
               
                 P903T 
                 0.64 
                 0.13 
                 0.52 
                 0.12 
                 0.39 
                 0.18 
                 Yes 
                 Yes 
               
               
                 P903A 
                 −0.22 
                 0.11 
                 −0.37 
                 0.10 
                 −0.12 
                 0.31 
                 No 
                 No 
               
               
                 P903R 
                 −1.86 
                 0.13 
                 −0.87 
                 0.09 
                 −0.31 
                 0.27 
                 No 
                 No 
               
               
                 P903C 
                 0.75 
                 0.15 
                 −0.71 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 P903E 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.05 
                 0.22 
                 Yes 
                 No 
               
               
                 P903G 
                 −1.37 
                 0.10 
                 −1.66 
                 0.10 
                 −0.49 
                 0.35 
                 No 
                 No 
               
               
                 P903H 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.04 
                 0.17 
                 Yes 
                 No 
               
               
                 P903L 
                 −0.52 
                 0.11 
                 −0.93 
                 0.12 
                 0.29 
                 0.10 
                 Yes 
                 No 
               
               
                 P903S 
                 −0.61 
                 0.12 
                 0.03 
                 0.10 
                 0.07 
                 0.22 
                 Yes 
                 No 
               
               
                 P903V 
                 −0.44 
                 0.12 
                 −0.77 
                 0.12 
                 0.25 
                 0.16 
                 Yes 
                 No 
               
               
                 I904A 
                 0.28 
                 0.05 
                 0.32 
                 0.05 
                 −0.01 
                 0.10 
                 Yes 
                 No 
               
               
                 I904R 
                 −0.52 
                 0.05 
                 −0.28 
                 0.04 
                 −0.14 
                 0.04 
                 No 
                 No 
               
               
                 I904N 
                 −0.26 
                 0.11 
                 0.07 
                 0.10 
                 −0.29 
                 0.13 
                 Yes 
                 No 
               
               
                 I904D 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.33 
                 0.37 
                 Yes 
                 No 
               
               
                 I904C 
                 −0.37 
                 0.09 
                 −0.06 
                 0.08 
                 0.16 
                 0.09 
                 Yes 
                 No 
               
               
                 I904Q 
                 −0.28 
                 0.11 
                 0.17 
                 0.10 
                 0.03 
                 0.37 
                 Yes 
                 No 
               
               
                 I904E 
                 −1.15 
                 0.08 
                 −1.73 
                 0.09 
                 −0.77 
                 0.30 
                 No 
                 No 
               
               
                 I904G 
                 −1.05 
                 0.04 
                 −0.45 
                 0.04 
                 −0.39 
                 0.03 
                 No 
                 No 
               
               
                 I904H 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.20 
                 0.48 
                 Yes 
                 No 
               
               
                 I904L 
                 −0.35 
                 0.07 
                 0.47 
                 0.06 
                 0.12 
                 0.09 
                 Yes 
                 No 
               
               
                 I904K 
                 −1.71 
                 0.15 
                 −0.48 
                 0.10 
                 0.05 
                 0.09 
                 Yes 
                 No 
               
               
                 I904M 
                 0.19 
                 0.08 
                 −0.04 
                 0.08 
                 0.03 
                 0.05 
                 Yes 
                 No 
               
               
                 I904F 
                 −0.71 
                 0.13 
                 0.38 
                 0.11 
                 0.15 
                 0.20 
                 Yes 
                 No 
               
               
                 I904S 
                 0.20 
                 0.04 
                 −0.09 
                 0.04 
                 0.07 
                 0.03 
                 Yes 
                 No 
               
               
                 I904* 
                 −1.37 
                 0.12 
                 −1.64 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I904T 
                 0.33 
                 0.07 
                 −0.20 
                 0.07 
                 −0.13 
                 0.08 
                 Yes 
                 No 
               
               
                 I904W 
                 −0.01 
                 0.06 
                 −0.07 
                 0.06 
                 −0.35 
                 0.24 
                 No 
                 No 
               
               
                 I904Y 
                 0.53 
                 0.12 
                 −0.47 
                 0.13 
                 0.01 
                 0.64 
                 Yes 
                 No 
               
               
                 I904V 
                 −0.13 
                 0.05 
                 0.08 
                 0.04 
                 0.00 
                 0.04 
                 Yes 
                 No 
               
               
                 I905A 
                 −0.31 
                 0.06 
                 −0.49 
                 0.06 
                 −0.02 
                 0.14 
                 No 
                 No 
               
               
                 I905R 
                 −1.93 
                 0.08 
                 −1.23 
                 0.06 
                 −1.47 
                 0.09 
                 No 
                 No 
               
               
                 I905N 
                 −0.95 
                 0.15 
                 −0.68 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I905D 
                 −1.69 
                 0.14 
                 −1.47 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I905C 
                 −0.01 
                 0.10 
                 0.49 
                 0.09 
                 −0.12 
                 0.11 
                 Yes 
                 No 
               
               
                 I905E 
                 −1.48 
                 0.10 
                 −2.09 
                 0.12 
                 −1.57 
                 0.43 
                 No 
                 No 
               
               
                 I905G 
                 −1.25 
                 0.05 
                 −0.83 
                 0.04 
                 −0.80 
                 0.04 
                 No 
                 No 
               
               
                 I905L 
                 −0.65 
                 0.07 
                 −0.31 
                 0.06 
                 −0.12 
                 0.07 
                 No 
                 No 
               
               
                 I905M 
                 0.15 
                 0.06 
                 −0.40 
                 0.07 
                 −0.10 
                 0.06 
                 Yes 
                 No 
               
               
                 I905F 
                 −0.10 
                 0.11 
                 −0.09 
                 0.11 
                 −0.55 
                 0.18 
                 No 
                 No 
               
               
                 I905S 
                 −1.01 
                 0.07 
                 −1.06 
                 0.07 
                 −0.63 
                 0.06 
                 No 
                 No 
               
               
                 I905T 
                 −0.17 
                 0.09 
                 −0.86 
                 0.09 
                 −0.52 
                 0.12 
                 No 
                 No 
               
               
                 I905W 
                 −1.31 
                 0.10 
                 −1.78 
                 0.11 
                 −1.43 
                 0.28 
                 No 
                 No 
               
               
                 I905V 
                 −0.18 
                 0.05 
                 −0.21 
                 0.05 
                 0.10 
                 0.06 
                 Yes 
                 No 
               
               
                 G906A 
                 0.41 
                 0.05 
                 0.56 
                 0.04 
                 0.42 
                 0.05 
                 Yes 
                 Yes 
               
               
                 G906S 
                 0.40 
                 0.05 
                 0.16 
                 0.05 
                 0.15 
                 0.06 
                 Yes 
                 Yes 
               
               
                 G906R 
                 −1.82 
                 0.06 
                 −2.39 
                 0.07 
                 −1.63 
                 0.08 
                 No 
                 No 
               
               
                 G906D 
                 −1.49 
                 0.10 
                 −1.05 
                 0.08 
                 −1.38 
                 0.18 
                 No 
                 No 
               
               
                 G906C 
                 −1.50 
                 0.11 
                 −1.21 
                 0.09 
                 −1.62 
                 0.11 
                 No 
                 No 
               
               
                 G906E 
                 −2.26 
                 0.12 
                 −1.63 
                 0.09 
                 −1.49 
                 0.11 
                 No 
                 No 
               
               
                 G906L 
                 −1.51 
                 0.09 
                 −2.32 
                 0.11 
                 −1.69 
                 0.27 
                 No 
                 No 
               
               
                 G906P 
                 −1.68 
                 0.12 
                 −1.05 
                 0.09 
                 −1.66 
                 0.10 
                 No 
                 No 
               
               
                 G906* 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.21 
                 0.40 
                 Yes 
                 No 
               
               
                 G906T 
                 −1.69 
                 0.11 
                 −2.68 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G906W 
                 −2.22 
                 0.11 
                 −1.14 
                 0.07 
                 −1.71 
                 0.08 
                 No 
                 No 
               
               
                 G906V 
                 −0.85 
                 0.05 
                 −1.20 
                 0.05 
                 −1.27 
                 0.06 
                 No 
                 No 
               
               
                 I907A 
                 0.70 
                 0.10 
                 0.42 
                 0.10 
                 0.27 
                 0.54 
                 Yes 
                 Yes 
               
               
                 I907V 
                 0.15 
                 0.07 
                 0.12 
                 0.07 
                 0.13 
                 0.06 
                 Yes 
                 Yes 
               
               
                 I907R 
                 −0.92 
                 0.08 
                 −1.15 
                 0.08 
                 −0.89 
                 0.09 
                 No 
                 No 
               
               
                 I907D 
                 −0.44 
                 0.17 
                 −0.97 
                 0.18 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I907C 
                 −0.16 
                 0.16 
                 0.84 
                 0.13 
                 0.12 
                 0.64 
                 Yes 
                 No 
               
               
                 I907E 
                 −1.06 
                 0.15 
                 −0.42 
                 0.12 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I907G 
                 −0.42 
                 0.06 
                 −0.40 
                 0.06 
                 −0.03 
                 0.06 
                 No 
                 No 
               
               
                 I907L 
                 0.34 
                 0.09 
                 0.24 
                 0.08 
                 −0.33 
                 0.09 
                 Yes 
                 No 
               
               
                 I907M 
                 NA 
                 NA 
                 NA 
                 NA 
                 0.12 
                 0.25 
                 Yes 
                 No 
               
               
                 I907F 
                 −0.50 
                 0.19 
                 −0.17 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 I907S 
                 −0.29 
                 0.03 
                 −0.18 
                 0.03 
                 0.25 
                 0.03 
                 Yes 
                 No 
               
               
                 I907T 
                 −0.44 
                 0.15 
                 0.78 
                 0.12 
                 0.28 
                 0.12 
                 Yes 
                 No 
               
               
                 D908A 
                 −2.26 
                 0.13 
                 −1.92 
                 0.11 
                 −1.10 
                 0.16 
                 No 
                 No 
               
               
                 D908R 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.53 
                 0.09 
                 Yes 
                 No 
               
               
                 D908N 
                 −0.27 
                 0.12 
                 −0.30 
                 0.12 
                 −0.70 
                 0.14 
                 No 
                 No 
               
               
                 D908E 
                 −1.61 
                 0.13 
                 −1.42 
                 0.11 
                 −1.11 
                 0.11 
                 No 
                 No 
               
               
                 D908G 
                 −2.25 
                 0.09 
                 −2.15 
                 0.08 
                 −1.77 
                 0.14 
                 No 
                 No 
               
               
                 D908S 
                 −1.92 
                 0.16 
                 −1.78 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D908W 
                 −1.93 
                 0.15 
                 −2.11 
                 0.15 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 D908Y 
                 0.26 
                 0.11 
                 −0.07 
                 0.12 
                 −0.15 
                 0.12 
                 Yes 
                 No 
               
               
                 D908V 
                 −1.74 
                 0.10 
                 −1.76 
                 0.10 
                 −1.52 
                 0.09 
                 No 
                 No 
               
               
                 R909A 
                 NA 
                 NA 
                 NA 
                 NA 
                 −1.45 
                 0.37 
                 Yes 
                 No 
               
               
                 R909Q 
                 −0.25 
                 0.18 
                 −0.94 
                 0.20 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R909G 
                 −1.30 
                 0.05 
                 −1.49 
                 0.05 
                 −1.38 
                 0.06 
                 No 
                 No 
               
               
                 R909K 
                 −0.87 
                 0.16 
                 −0.60 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R909S 
                 −1.08 
                 0.10 
                 −0.84 
                 0.09 
                 −0.58 
                 0.12 
                 No 
                 No 
               
               
                 R909T 
                 −1.28 
                 0.15 
                 −0.89 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R909W 
                 −0.96 
                 0.10 
                 −1.94 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R909V 
                 −1.36 
                 0.11 
                 −2.33 
                 0.14 
                 −1.34 
                 0.47 
                 No 
                 No 
               
               
                 G910R 
                 −1.03 
                 0.08 
                 −1.62 
                 0.09 
                 −1.75 
                 0.16 
                 No 
                 No 
               
               
                 G910D 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.69 
                 0.19 
                 Yes 
                 No 
               
               
                 G910C 
                 −0.91 
                 0.13 
                 −1.29 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G910S 
                 −1.15 
                 0.10 
                 −1.28 
                 0.10 
                 −1.41 
                 0.19 
                 No 
                 No 
               
               
                 G910W 
                 −1.93 
                 0.15 
                 −1.82 
                 0.13 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 G910V 
                 −1.34 
                 0.08 
                 −1.15 
                 0.07 
                 −0.66 
                 0.13 
                 No 
                 No 
               
               
                 E911A 
                 −0.79 
                 0.12 
                 −1.56 
                 0.14 
                 −0.93 
                 0.10 
                 No 
                 No 
               
               
                 E911R 
                 −1.42 
                 0.12 
                 −2.19 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 E911D 
                 −0.45 
                 0.14 
                 −0.47 
                 0.13 
                 −0.18 
                 0.25 
                 No 
                 No 
               
               
                 E911G 
                 −0.65 
                 0.06 
                 −0.80 
                 0.06 
                 −0.83 
                 0.08 
                 No 
                 No 
               
               
                 E911L 
                 NA 
                 NA 
                 NA 
                 NA 
                 −0.50 
                 0.15 
                 Yes 
                 No 
               
               
                 E911K 
                 −0.39 
                 0.13 
                 −0.14 
                 0.12 
                 −0.57 
                 0.15 
                 No 
                 No 
               
               
                 E911* 
                 −0.20 
                 0.11 
                 0.12 
                 0.10 
                 −0.18 
                 0.16 
                 Yes 
                 No 
               
               
                 E911V 
                 −0.21 
                 0.08 
                 −0.62 
                 0.08 
                 −0.61 
                 0.09 
                 No 
                 No 
               
               
                 R912A 
                 0.46 
                 0.09 
                 0.49 
                 0.09 
                 0.31 
                 0.64 
                 Yes 
                 Yes 
               
               
                 R912L 
                 0.53 
                 0.08 
                 0.38 
                 0.08 
                 0.21 
                 0.16 
                 Yes 
                 Yes 
               
               
                 R912S 
                 1.04 
                 0.11 
                 0.30 
                 0.11 
                 0.31 
                 0.54 
                 Yes 
                 Yes 
               
               
                 R912V 
                 0.19 
                 0.09 
                 0.23 
                 0.09 
                 0.03 
                 0.09 
                 Yes 
                 Yes 
               
               
                 R912C 
                 0.43 
                 0.15 
                 0.54 
                 0.15 
                 −0.29 
                 0.16 
                 Yes 
                 No 
               
               
                 R912Q 
                 0.22 
                 0.05 
                 0.15 
                 0.05 
                 −0.05 
                 0.09 
                 Yes 
                 No 
               
               
                 R912E 
                 0.53 
                 0.12 
                 −0.67 
                 0.14 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 R912G 
                 −0.21 
                 0.05 
                 −1.04 
                 0.06 
                 −0.56 
                 0.05 
                 No 
                 No 
               
               
                 R912P 
                 0.53 
                 0.09 
                 0.79 
                 0.09 
                 −0.40 
                 0.14 
                 Yes 
                 No 
               
               
                 R912T 
                 −0.54 
                 0.17 
                 −0.07 
                 0.15 
                 0.52 
                 0.65 
                 Yes 
                 No 
               
               
                 R912W 
                 −0.09 
                 0.07 
                 −0.14 
                 0.07 
                 −0.43 
                 0.10 
                 No 
                 No 
               
               
                 N913A 
                 −1.19 
                 0.13 
                 −0.97 
                 0.11 
                 −0.87 
                 0.33 
                 No 
                 No 
               
               
                 N913R 
                 −2.49 
                 0.14 
                 −0.64 
                 0.07 
                 −1.67 
                 0.40 
                 No 
                 No 
               
               
                 N913D 
                 −0.62 
                 0.13 
                 −0.44 
                 0.12 
                 −0.75 
                 0.10 
                 No 
                 No 
               
               
                 N913E 
                 −0.91 
                 0.12 
                 −1.92 
                 0.16 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N913G 
                 −1.34 
                 0.07 
                 −0.91 
                 0.06 
                 −1.56 
                 0.30 
                 No 
                 No 
               
               
                 N913H 
                 0.12 
                 0.07 
                 0.13 
                 0.07 
                 −0.20 
                 0.12 
                 Yes 
                 No 
               
               
                 N913I 
                 −0.16 
                 0.09 
                 −0.18 
                 0.09 
                 −0.18 
                 0.12 
                 No 
                 No 
               
               
                 N913L 
                 −0.39 
                 0.11 
                 −0.72 
                 0.11 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N913K 
                 −0.37 
                 0.05 
                 −0.29 
                 0.04 
                 −0.27 
                 0.08 
                 No 
                 No 
               
               
                 N913S 
                 −0.29 
                 0.08 
                 −0.06 
                 0.07 
                 −0.20 
                 0.12 
                 No 
                 No 
               
               
                 N913T 
                 0.09 
                 0.11 
                 −0.67 
                 0.12 
                 −0.35 
                 0.24 
                 Yes 
                 No 
               
               
                 N913Y 
                 −0.47 
                 0.18 
                 −0.44 
                 0.17 
                 NA 
                 NA 
                 Yes 
                 No 
               
               
                 N913V 
                 −1.32 
                 0.12 
                 −0.89 
                 0.10 
                 −1.09 
                 0.18 
                 No 
                 No 
               
               
                   
               
               
                   1 Key to Header abbreviations: Mutants are defined by single letter amino acid (wild-type) at a given position in the wild-type AsCas12a polypeptide (e.g., amino acid position 500), followed by the variant amino acid change thereafter; “Enrich. Score (1)” refers to Enrichment score of the variant in a Condition 1 background; “Stand. Error (1) refers to the Standard error for experiments conducted for a given variant in a Condition 1 background; “Enrich. Score (2)” refers to Enrichment Score of the variant in a Condition 2 background; “Stand. Error (2) refers to the Standard Error for experiments conducted for a given variant in a Condition 2 background; “Enrich. Score (3)”refers to Enrichment Score of the variant in a Condition 3 background; “Stand. Error (3) refers to the Standard Error for experiments conducted for a given variant in a Condition 3 background; “Any Positive Enrichment?” refers to the occurrence of positive enrichment for a given variant under at least one experimental Condition background; “Consistent positive enrichment?” refers to the occurrence of positive enrichment for a given variant under all tested experimental Condition backgrounds. 
               
            
           
         
       
     
     One hundred eighty-seven (187) variants (˜6% of total) consistently enhanced the survival rate under all conditions (Table 4). These variants, including the four validated individually, can be stacked on the WT- or M537R/F870L-AsCas12a, to boost its DNA cleavage activity at TTTT-PAM. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Point mutations consistently enriched over the reference proteins 
               
               
                 under all conditions. 1   
               
            
           
           
               
               
               
               
               
               
            
               
                 SEQ ID 
                   
                   
                 Variant score 
                 Variant score 
                 Variant score 
               
               
                 NO.: 
                 Mutant 
                 Position 
                 (condition 1) 
                 (condition 2) 
                 (condition 3) 
               
               
                   
               
               
                  59 
                 R499C 
                 499 
                 0.14 ± 0.08 
                  0.6 ± 0.07 
                 0.06 ± 0.1  
               
               
                  60 
                 R499L 
                 499 
                 0.08 ± 0.05 
                 0.05 ± 0.06 
                 0.09 ± 0.15 
               
               
                  61 
                 R499K 
                 499 
                 0.54 ± 0.06 
                 0.23 ± 0.06 
                 0.38 ± 0.1  
               
               
                  62 
                 L500M 
                 500 
                 0.01 ± 0.05 
                  0.3 ± 0.05 
                 0.28 ± 0.12 
               
               
                  63 
                 T501L 
                 501 
                 0.18 ± 0.04 
                 0.32 ± 0.04 
                 0.12 ± 0.07 
               
               
                  64 
                 T501M 
                 501 
                 0.32 ± 0.07 
                 0.35 ± 0.07 
                 0.17 ± 0.29 
               
               
                  65 
                 T501V 
                 501 
                 0.22 ± 0.06 
                 0.29 ± 0.06 
                 0.13 ± 0.2  
               
               
                  66 
                 G502R 
                 502 
                 0.14 ± 0.05 
                 0.28 ± 0.05 
                 0.98 ± 0.07 
               
               
                  67 
                 G502E 
                 502 
                 0.42 ± 0.08 
                 0.17 ± 0.08 
                 0.19 ± 0.3  
               
               
                  68 
                 G502L 
                 502 
                 0.45 ± 0.07 
                  0.1 ± 0.07 
                   0 ± 0.11 
               
               
                  69 
                 G502S 
                 502 
                 0.08 ± 0.06 
                 0.23 ± 0.06 
                 0.16 ± 0.12 
               
               
                  70 
                 G502W 
                 502 
                 0.14 ± 0.07 
                 0.65 ± 0.06 
                 0.36 ± 0.14 
               
               
                  71 
                 G502V 
                 502 
                 0.21 ± 0.05 
                 0.21 ± 0.05 
                 0.13 ± 0.07 
               
               
                  72 
                 L505A 
                 505 
                 0.61 ± 0.05 
                  0.5 ± 0.05 
                 0.47 ± 0.13 
               
               
                  73 
                 L505R 
                 505 
                  0.4 ± 0.03 
                 0.56 ± 0.03 
                 0.81 ± 0.05 
               
               
                  74 
                 L505Q 
                 505 
                  0.3 ± 0.07 
                 0.82 ± 0.07 
                 0.16 ± 0.11 
               
               
                  75 
                 L505E 
                 505 
                 0.18 ± 0.06 
                 0.03 ± 0.07 
                 0.14 ± 0.21 
               
               
                  76 
                 L505G 
                 505 
                 0.18 ± 0.03 
                 0.72 ± 0.03 
                  0.4 ± 0.05 
               
               
                  77 
                 L505H 
                 505 
                 0.33 ± 0.11 
                 0.83 ± 0.1  
                 0.34 ± 0.32 
               
               
                  78 
                 L505K 
                 505 
                 0.02 ± 0.1  
                   1 ± 0.08 
                   1 ± 0.13 
               
               
                  79 
                 L505S 
                 505 
                 0.13 ± 0.06 
                 0.32 ± 0.06 
                  0.6 ± 0.07 
               
               
                  80 
                 E506A 
                 506 
                 0.33 ± 0.03 
                 0.47 ± 0.03 
                  0.7 ± 0.05 
               
               
                  81 
                 E506R 
                 506 
                 0.46 ± 0.03 
                 0.81 ± 0.03 
                  1.2 ± 0.04 
               
               
                  82 
                 E506N 
                 506 
                 0.24 ± 0.09 
                 0.53 ± 0.09 
                  0.5 ± 0.29 
               
               
                  83 
                 E506C 
                 506 
                  0.2 ± 0.06 
                 0.29 ± 0.06 
                 0.49 ± 0.19 
               
               
                  84 
                 E506Q 
                 506 
                 0.09 ± 0.07 
                 0.74 ± 0.06 
                 0.33 ± 0.15 
               
               
                  85 
                 E506G 
                 506 
                 0.24 ± 0.02 
                 0.39 ± 0.02 
                 0.53 ± 0.03 
               
               
                  86 
                 E506H 
                 506 
                 0.35 ± 0.09 
                 0.1 ± 0.1 
                 0.98 ± 0.31 
               
               
                  87 
                 E506I 
                 506 
                 0.47 ± 0.09 
                 0.45 ± 0.09 
                 0.69 ± 0.13 
               
               
                  88 
                 E506L 
                 506 
                  0.3 ± 0.04 
                 0.61 ± 0.04 
                 0.56 ± 0.07 
               
               
                  89 
                 E506K 
                 506 
                 0.18 ± 0.06 
                 0.59 ± 0.05 
                 1.08 ± 0.08 
               
               
                  90 
                 E506M 
                 506 
                 0.53 ± 0.06 
                 0.28 ± 0.07 
                 0.47 ± 0.17 
               
               
                  91 
                 E506S 
                 506 
                 0.01 ± 0.05 
                 0.47 ± 0.04 
                  0.5 ± 0.06 
               
               
                  92 
                 E506T 
                 506 
                 0.39 ± 0.06 
                 0.12 ± 0.07 
                  0.9 ± 0.23 
               
               
                  93 
                 E506Y 
                 506 
                 0.16 ± 0.09 
                 0.29 ± 0.09 
                 0.43 ± 0.25 
               
               
                  94 
                 E506V 
                 506 
                 0.45 ± 0.03 
                 0.51 ± 0.03 
                 0.75 ± 0.05 
               
               
                  95 
                 E508A 
                 508 
                 0.36 ± 0.03 
                  0.2 ± 0.03 
                 0.18 ± 0.06 
               
               
                  96 
                 E508R 
                 508 
                 0.54 ± 0.03 
                  0.8 ± 0.03 
                 0.82 ± 0.06 
               
               
                  97 
                 E508Q 
                 508 
                 0.25 ± 0.06 
                 0.11 ± 0.07 
                 0.51 ± 0.13 
               
               
                  98 
                 E508G 
                 508 
                 0.16 ± 0.02 
                 0.17 ± 0.02 
                 0.22 ± 0.04 
               
               
                  99 
                 E508L 
                 508 
                 0.03 ± 0.04 
                  0.1 ± 0.04 
                 0.26 ± 0.11 
               
               
                 100 
                 E508K 
                 508 
                  0.2 ± 0.06 
                 0.49 ± 0.06 
                 0.66 ± 0.08 
               
               
                 101 
                 E508M 
                 508 
                 0.25 ± 0.07 
                 0.57 ± 0.06 
                 0.54 ± 0.11 
               
               
                 102 
                 E508F 
                 508 
                 0.27 ± 0.08 
                 0.19 ± 0.08 
                 0.39 ± 0.29 
               
               
                 103 
                 E508S 
                 508 
                 0.31 ± 0.05 
                 0.62 ± 0.04 
                 0.34 ± 0.06 
               
               
                 104 
                 E508T 
                 508 
                 0.19 ± 0.06 
                 0.73 ± 0.06 
                 0.55 ± 0.1  
               
               
                 105 
                 E508Y 
                 508 
                 0.35 ± 0.09 
                 0.19 ± 0.1  
                 0.21 ± 0.27 
               
               
                 106 
                 E508V 
                 508 
                 0.16 ± 0.03 
                 0.22 ± 0.03 
                 0.34 ± 0.05 
               
               
                 107 
                 P509R 
                 509 
                 0.23 ± 0.03 
                 0.27 ± 0.03 
                 1.04 ± 0.05 
               
               
                 108 
                 P509K 
                 509 
                 0.01 ± 0.07 
                 0.12 ± 0.07 
                 1.29 ± 0.13 
               
               
                 109 
                 P509M 
                 509 
                 0.34 ± 0.07 
                 0.34 ± 0.07 
                  0.1 ± 0.22 
               
               
                 110 
                 P509S 
                 509 
                  0.1 ± 0.04 
                 0.14 ± 0.04 
                 0.14 ± 0.1  
               
               
                 111 
                 P509W 
                 509 
                 0.04 ± 0.05 
                 0.33 ± 0.05 
                 0.61 ± 0.18 
               
               
                 112 
                 P509Y 
                 509 
                 0.18 ± 0.09 
                  0.2 ± 0.09 
                 0.53 ± 0.3  
               
               
                 113 
                 S510G 
                 510 
                 0.18 ± 0.03 
                 0.49 ± 0.03 
                 0.21 ± 0.06 
               
               
                 114 
                 S510L 
                 510 
                 0.57 ± 0.06 
                 0.72 ± 0.06 
                 0.74 ± 0.09 
               
               
                 115 
                 S512R 
                 512 
                 0.07 ± 0.07 
                 0.34 ± 0.07 
                 0.07 ± 0.19 
               
               
                 116 
                 F513L 
                 513 
                 0.53 ± 0.04 
                 0.63 ± 0.04 
                 0.41 ± 0.07 
               
               
                 117 
                 F513W 
                 513 
                 0.04 ± 0.06 
                 0.35 ± 0.06 
                 0.28 ± 0.13 
               
               
                 118 
                 N515A 
                 515 
                  0.6 ± 0.06 
                 0.82 ± 0.06 
                 0.12 ± 0.11 
               
               
                 119 
                 N515R 
                 515 
                 0.63 ± 0.06 
                 0.82 ± 0.05 
                 0.19 ± 0.11 
               
               
                 120 
                 N515I 
                 515 
                 0.23 ± 0.07 
                  0.3 ± 0.07 
                 0.16 ± 0.14 
               
               
                 121 
                 N515L 
                 515 
                 0.33 ± 0.06 
                 0.53 ± 0.06 
                 0.07 ± 0.2  
               
               
                 122 
                 N515T 
                 515 
                 0.41 ± 0.08 
                 0.14 ± 0.08 
                 0.29 ± 0.16 
               
               
                 123 
                 N515V 
                 515 
                  0.5 ± 0.05 
                 0.49 ± 0.05 
                 0.45 ± 0.09 
               
               
                 124 
                 K516R 
                 516 
                 0.01 ± 0.03 
                 0.26 ± 0.03 
                  0.4 ± 0.06 
               
               
                 125 
                 R518K 
                 518 
                  0.2 ± 0.09 
                 0.72 ± 0.08 
                 0.05 ± 0.17 
               
               
                 126 
                 T522L 
                 522 
                  1.1 ± 0.05 
                 0.92 ± 0.05 
                 0.28 ± 0.1  
               
               
                 127 
                 T522M 
                 522 
                 0.92 ± 0.07 
                 0.81 ± 0.08 
                 0.53 ± 0.21 
               
               
                 128 
                 T522V 
                 522 
                 0.16 ± 0.05 
                 0.28 ± 0.05 
                 0.04 ± 0.07 
               
               
                 129 
                 K523R 
                 523 
                 0.17 ± 0.02 
                 0.37 ± 0.02 
                   0 ± 0.03 
               
               
                 130 
                 S527D 
                 527 
                 0.13 ± 0.11 
                 0.01 ± 0.11 
                 0.34 ± 0.41 
               
               
                 131 
                 V528D 
                 528 
                 0.01 ± 0.07 
                 0.27 ± 0.07 
                 0.12 ± 0.12 
               
               
                 132 
                 V528L 
                 528 
                 0.55 ± 0.03 
                 0.59 ± 0.03 
                 0.31 ± 0.07 
               
               
                 133 
                 V528M 
                 528 
                 0.19 ± 0.05 
                 0.02 ± 0.05 
                 0.13 ± 0.1  
               
               
                 134 
                 S542N 
                 542 
                 0.24 ± 0.09 
                 0.02 ± 0.09 
                 0.29 ± 0.07 
               
               
                 135 
                 S542C 
                 542 
                 0.03 ± 0.17 
                 0.15 ± 0.17 
                 0.42 ± 0.16 
               
               
                 136 
                 K550R 
                 550 
                 0.05 ± 0.03 
                 0.18 ± 0.03 
                 0.17 ± 0.07 
               
               
                 137 
                 N551D 
                 551 
                 0.14 ± 0.04 
                 0.15 ± 0.04 
                 0.67 ± 0.07 
               
               
                 138 
                 A554I 
                 554 
                 0.15 ± 0.09 
                 0.71 ± 0.08 
                 0.39 ± 0.34 
               
               
                 139 
                 A554T 
                 554 
                 0.45 ± 0.04 
                 0.32 ± 0.05 
                 0.93 ± 0.07 
               
               
                 140 
                 A554V 
                 554 
                 0.57 ± 0.03 
                 0.48 ± 0.03 
                 0.54 ± 0.04 
               
               
                 141 
                 I555V 
                 555 
                 0.41 ± 0.03 
                 0.13 ± 0.03 
                 0.14 ± 0.06 
               
               
                 142 
                 L556M 
                 556 
                 0.08 ± 0.08 
                  0.1 ± 0.08 
                 0.11 ± 0.21 
               
               
                 143 
                 V558M 
                 558 
                 0.24 ± 0.06 
                 0.15 ± 0.06 
                  0.1 ± 0.12 
               
               
                 144 
                 K559A 
                 559 
                 0.17 ± 0.04 
                 0.08 ± 0.04 
                 0.13 ± 0.08 
               
               
                 145 
                 N560A 
                 560 
                 0.34 ± 0.05 
                 0.18 ± 0.05 
                 0.18 ± 0.08 
               
               
                 146 
                 N560D 
                 560 
                 0.16 ± 0.04 
                 0.18 ± 0.04 
                 0.16 ± 0.08 
               
               
                 147 
                 N560E 
                 560 
                 0.48 ± 0.06 
                 0.28 ± 0.06 
                 0.11 ± 0.25 
               
               
                 148 
                 N560M 
                 560 
                 0.16 ± 0.09 
                 0.31 ± 0.09 
                 0.18 ± 0.13 
               
               
                 149 
                 P569D 
                 569 
                  0.6 ± 0.08 
                 0.33 ± 0.08 
                 1.25 ± 0.11 
               
               
                 150 
                 Q571A 
                 571 
                 0.64 ± 0.07 
                 0.39 ± 0.08 
                 1.09 ± 0.23 
               
               
                 151 
                 Q571P 
                 571 
                 0.17 ± 0.07 
                 0.61 ± 0.07 
                 0.13 ± 0.14 
               
               
                 152 
                 Q571S 
                 571 
                 0.25 ± 0.09 
                  0.2 ± 0.09 
                 0.89 ± 0.23 
               
               
                 153 
                 Q571T 
                 571 
                 0.22 ± 0.13 
                 0.19 ± 0.13 
                 0.87 ± 0.41 
               
               
                 154 
                 K572E 
                 572 
                 0.11 ± 0.04 
                 0.25 ± 0.04 
                 0.42 ± 0.08 
               
               
                 155 
                 Y575G 
                 575 
                 0.53 ± 0.04 
                 0.21 ± 0.04 
                 0.32 ± 0.07 
               
               
                 156 
                 Y575M 
                 575 
                 0.89 ± 0.11 
                 0.27 ± 0.12 
                 0.31 ± 0.41 
               
               
                 157 
                 K576C 
                 576 
                 0.27 ± 0.07 
                 0.25 ± 0.07 
                  0.1 ± 0.26 
               
               
                 158 
                 S579T 
                 579 
                 0.17 ± 0.04 
                 0.33 ± 0.04 
                 0.01 ± 0.06 
               
               
                 159 
                 S579V 
                 579 
                 0.04 ± 0.03 
                 0.02 ± 0.03 
                 0.05 ± 0.07 
               
               
                 160 
                 T583I 
                 583 
                 0.04 ± 0.08 
                 0.11 ± 0.07 
                 0.07 ± 0.17 
               
               
                 161 
                 E584H 
                 584 
                 0.09 ± 0.07 
                 0.22 ± 0.07 
                 0.17 ± 0.14 
               
               
                 162 
                 E584V 
                 584 
                  0.1 ± 0.03 
                 0.06 ± 0.03 
                 0.12 ± 0.04 
               
               
                 163 
                 K585R 
                 585 
                 0.07 ± 0.03 
                 0.32 ± 0.03 
                 0.06 ± 0.05 
               
               
                 164 
                 K585F 
                 585 
                 0.51 ± 0.09 
                 0.04 ± 0.09 
                 0.61 ± 0.36 
               
               
                 165 
                 D596E 
                 596 
                 0.04 ± 0.04 
                 0.24 ± 0.04 
                 0.69 ± 0.05 
               
               
                 166 
                 P599G 
                 599 
                 0.84 ± 0.04 
                 0.83 ± 0.04 
                 1.01 ± 0.05 
               
               
                 167 
                 A602C 
                 602 
                 0.64 ± 0.09 
                 0.61 ± 0.09 
                 0.73 ± 0.28 
               
               
                 168 
                 L612M 
                 612 
                  0.7 ± 0.07 
                  0.7 ± 0.07 
                 0.01 ± 0.03 
               
               
                 169 
                 A614R 
                 614 
                 0.28 ± 0.04 
                 0.07 ± 0.05 
                 0.16 ± 0.05 
               
               
                 170 
                 A614I 
                 614 
                 0.52 ± 0.11 
                 0.59 ± 0.11 
                 0.41 ± 0.22 
               
               
                 171 
                 T616A 
                 616 
                 0.32 ± 0.03 
                 0.24 ± 0.04 
                 0.09 ± 0.05 
               
               
                 172 
                 T616R 
                 616 
                 0.19 ± 0.03 
                 0.12 ± 0.03 
                 0.62 ± 0.04 
               
               
                 173 
                 T616Q 
                 616 
                 0.35 ± 0.07 
                 0.38 ± 0.07 
                 0.78 ± 0.2  
               
               
                 174 
                 T616G 
                 616 
                 0.22 ± 0.03 
                 0.01 ± 0.03 
                 0.16 ± 0.06 
               
               
                 175 
                 T616Y 
                 616 
                 0.54 ± 0.09 
                 0.64 ± 0.09 
                 0.05 ± 0.38 
               
               
                 176 
                 A617G 
                 617 
                 0.03 ± 0.03 
                 0.05 ± 0.03 
                 0.24 ± 0.06 
               
               
                 177 
                 F619M 
                 619 
                 0.12 ± 0.07 
                 0.55 ± 0.07 
                 0.22 ± 0.25 
               
               
                 178 
                 Q620A 
                 620 
                 0.22 ± 0.04 
                   0 ± 0.05 
                 0.18 ± 0.09 
               
               
                 179 
                 Q620R 
                 620 
                 0.25 ± 0.03 
                 0.18 ± 0.03 
                 0.17 ± 0.04 
               
               
                 180 
                 Q620N 
                 620 
                 0.26 ± 0.14 
                 0.28 ± 0.14 
                 0.36 ± 0.21 
               
               
                 181 
                 Q620L 
                 620 
                 0.14 ± 0.04 
                 0.45 ± 0.04 
                  0.4 ± 0.16 
               
               
                 182 
                 Q620K 
                 620 
                  0.1 ± 0.07 
                 0.24 ± 0.07 
                 0.04 ± 0.1  
               
               
                 183 
                 T621A 
                 621 
                 0.18 ± 0.04 
                 0.13 ± 0.04 
                 0.17 ± 0.1  
               
               
                 184 
                 H622G 
                 622 
                 0.05 ± 0.03 
                 0.18 ± 0.03 
                 0.07 ± 0.06 
               
               
                 185 
                 H622S 
                 622 
                 0.16 ± 0.06 
                 0.59 ± 0.06 
                 0.08 ± 0.1  
               
               
                 186 
                 H622T 
                 622 
                 0.01 ± 0.09 
                 0.84 ± 0.08 
                 0.31 ± 0.34 
               
               
                 187 
                 H622V 
                 622 
                 0.18 ± 0.05 
                 0.15 ± 0.05 
                 0.31 ± 0.12 
               
               
                 188 
                 T623E 
                 623 
                 0.32 ± 0.05 
                 0.23 ± 0.05 
                 0.02 ± 0.05 
               
               
                 189 
                 T623H 
                 623 
                 0.6 ± 0.1 
                 0.01 ± 0.11 
                 0.58 ± 0.55 
               
               
                 190 
                 T623L 
                 623 
                 0.33 ± 0.05 
                 0.18 ± 0.05 
                 0.17 ± 0.16 
               
               
                 191 
                 T623M 
                 623 
                 0.21 ± 0.07 
                 0.28 ± 0.07 
                 0.59 ± 0.22 
               
               
                 192 
                 T623F 
                 623 
                 0.8 ± 0.1 
                 0.61 ± 0.1  
                 0.47 ± 0.32 
               
               
                 193 
                 T624P 
                 624 
                 0.92 ± 0.02 
                 0.92 ± 0.02 
                 0.04 ± 0.03 
               
               
                 194 
                 L627C 
                 627 
                 0.14 ± 0.13 
                 0.84 ± 0.11 
                 0.57 ± 0.48 
               
               
                 195 
                 L628C 
                 628 
                 0.31 ± 0.09 
                 0.1 ± 0.1 
                 0.29 ± 0.31 
               
               
                 196 
                 L628W 
                 628 
                 0.25 ± 0.06 
                 0.01 ± 0.07 
                 0.67 ± 0.15 
               
               
                 197 
                 N630R 
                 630 
                 0.53 ± 0.05 
                 0.06 ± 0.06 
                 0.94 ± 0.08 
               
               
                 198 
                 I633N 
                 633 
                 0.16 ± 0.06 
                 0.65 ± 0.06 
                 0.15 ± 0.1  
               
               
                 199 
                 I633M 
                 633 
                 0.17 ± 0.07 
                 0.28 ± 0.07 
                  0.1 ± 0.19 
               
               
                 200 
                 I633S 
                 633 
                 0.02 ± 0.04 
                 0.35 ± 0.04 
                 0.22 ± 0.08 
               
               
                 201 
                 E634N 
                 634 
                 0.52 ± 0.12 
                 0.46 ± 0.12 
                   0 ± 0.36 
               
               
                 202 
                 P635A 
                 635 
                 0.04 ± 0.05 
                 0.29 ± 0.05 
                 0.59 ± 0.07 
               
               
                 203 
                 P635D 
                 635 
                 0.14 ± 0.09 
                 0.49 ± 0.09 
                 0.52 ± 0.14 
               
               
                 204 
                 P635E 
                 635 
                 0.51 ± 0.06 
                 0.49 ± 0.06 
                  0.7 ± 0.16 
               
               
                 205 
                 P635T 
                 635 
                 0.36 ± 0.06 
                 0.06 ± 0.06 
                 0.01 ± 0.08 
               
               
                 206 
                 T639G 
                 639 
                 0.52 ± 0.06 
                 0.44 ± 0.06 
                 0.06 ± 0.23 
               
               
                 207 
                 D840S 
                 840 
                 0.37 ± 0.08 
                 0.33 ± 0.08 
                  0.1 ± 0.16 
               
               
                 208 
                 A842S 
                 842 
                 0.36 ± 0.06 
                 0.08 ± 0.06 
                 0.04 ± 0.1  
               
               
                 209 
                 A844E 
                 844 
                 0.38 ± 0.1  
                 0.06 ± 0. 1 
                 0.13 ± 0.21 
               
               
                 210 
                 T851A 
                 851 
                 0.41 ± 0.06 
                 0.14 ± 0.06 
                 0.08 ± 0.1  
               
               
                 211 
                 T851V 
                 851 
                 0.32 ± 0.06 
                 0.13 ± 0.06 
                 0.54 ± 0.07 
               
               
                 212 
                 E853V 
                 853 
                 0.14 ± 0.07 
                  0.1 ± 0.07 
                 0.38 ± 0.09 
               
               
                 213 
                 R862K 
                 862 
                 0.04 ± 0.14 
                 0.54 ± 0.13 
                 0.02 ± 0.38 
               
               
                 214 
                 S866F 
                 866 
                   0 ± 0.13 
                 0.06 ± 0.12 
                  0.1 ± 0.14 
               
               
                 215 
                 S866T 
                 866 
                 0.05 ± 0.13 
                 0.02 ± 0.13 
                  0.4 ± 0.15 
               
               
                 216 
                 V873A 
                 873 
                 0.16 ± 0.11 
                 0.05 ± 0.11 
                 0.08 ± 0.16 
               
               
                 217 
                 N878D 
                 878 
                 0.03 ± 0.06 
                 0.02 ± 0.06 
                 0.04 ± 0.08 
               
               
                 218 
                 Q880R 
                 880 
                 0.13 ± 0.05 
                 0.02 ± 0.05 
                 0.01 ± 0.06 
               
               
                 219 
                 Q880G 
                 880 
                 0.25 ± 0.04 
                 0.19 ± 0.04 
                 0.64 ± 0.05 
               
               
                 220 
                 A882D 
                 882 
                 0.32 ± 0.05 
                 0.22 ± 0.05 
                  0.1 ± 0.07 
               
               
                 221 
                 A882S 
                 882 
                 0.11 ± 0.12 
                 0.14 ± 0.11 
                 0.23 ± 0.22 
               
               
                 222 
                 N883G 
                 883 
                 0.42 ± 0.08 
                 0.37 ± 0.08 
                 0.03 ± 0.11 
               
               
                 223 
                 N883K 
                 883 
                 0.12 ± 0.16 
                 0.23 ± 0.16 
                 0.16 ± 0.1  
               
               
                 224 
                 S884V 
                 884 
                 0.05 ± 0.11 
                 0.61 ± 0.1  
                 0.03 ± 0.14 
               
               
                 225 
                 S886L 
                 886 
                 0.09 ± 0.08 
                 0.12 ± 0.08 
                 0.05 ± 0.11 
               
               
                 226 
                 S886M 
                 886 
                 0.32 ± 0.11 
                 0.15 ± 0.11 
                  0.4 ± 0.35 
               
               
                 227 
                 S886W 
                 886 
                 0.23 ± 0.07 
                 0.01 ± 0.07 
                  0.7 ± 0.19 
               
               
                 228 
                 Q890C 
                 890 
                 0.03 ± 0.11 
                 0.64 ± 0.1  
                 0.08 ± 0.54 
               
               
                 229 
                 Q890H 
                 890 
                 0.39 ± 0.09 
                 0.07 ± 0.09 
                 0.04 ± 0.11 
               
               
                 230 
                 Q890W 
                 890 
                 0.03 ± 0.08 
                 0.23 ± 0.07 
                 0.03 ± 0.08 
               
               
                 231 
                 A894R 
                 894 
                 0.19 ± 0.06 
                 0.06 ± 0.06 
                 0.04 ± 0.08 
               
               
                 232 
                 A894D 
                 894 
                 0.04 ± 0.06 
                 0.09 ± 0.06 
                 0.21 ± 0.05 
               
               
                 233 
                 Y895D 
                 895 
                 0.16 ± 0.04 
                   0 ± 0.04 
                 0.09 ± 0.04 
               
               
                 234 
                 H899A 
                 899 
                 0.21 ± 0.08 
                 0.16 ± 0.07 
                 0.01 ± 0.48 
               
               
                 235 
                 H899N 
                 899 
                 0.15 ± 0.15 
                  0.7 ± 0.14 
                 0.08 ± 0.18 
               
               
                 236 
                 E901D 
                 901 
                 0.07 ± 0.1  
                 0.05 ± 0.1  
                 0.14 ± 0.15 
               
               
                 237 
                 P903T 
                 903 
                 0.64 ± 0.13 
                 0.52 ± 0.12 
                 0.39 ± 0.18 
               
               
                 328 
                 G906A 
                 906 
                 0.41 ± 0.05 
                 0.56 ± 0.04 
                 0.42 ± 0.05 
               
               
                 239 
                 G906S 
                 906 
                  0.4 ± 0.05 
                 0.16 ± 0.05 
                 0.15 ± 0.06 
               
               
                 240 
                 1907A 
                 907 
                 0.7 ± 0.1 
                 0.42 ± 0.1  
                 0.27 ± 0.54 
               
               
                 241 
                 1907V 
                 907 
                 0.15 ± 0.07 
                 0.12 ± 0.07 
                 0.13 ± 0.06 
               
               
                 242 
                 R912A 
                 912 
                 0.46 ± 0.09 
                 0.49 ± 0.09 
                 0.31 ± 0.64 
               
               
                 243 
                 R912L 
                 912 
                 0.53 ± 0.08 
                 0.38 ± 0.08 
                 0.21 ± 0.16 
               
               
                 244 
                 R912S 
                 912 
                 1.04 ± 0.11 
                  0.3 ± 0.11 
                 0.31 ± 0.54 
               
               
                 245 
                 R912V 
                 912 
                 0.19 ± 0.09 
                 0.23 ± 0.09 
                 0.03 ± 0.09 
               
               
                   
               
               
                   1 The phenotype scores (i.e. natural logarithm of relative enrichment) of each point mutation are provided. The error bar estimates the precision of the measurement, which is dependent on the sequencing count of each variant in the libraries. Only variants with counts greater than 50 in all libraries were included in the analysis. 
               
            
           
         
       
     
     Table 5 shows the sequences used as primers to generate the AsCas12a saturation mutagenesis library. Standard recombinant methods and techniques were used. The screening library was constructed using the method described in Wrenbeck et al. (2016). 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Primer sequences to generate AsCas12a saturation mutagenesis library. 
               
            
           
           
               
               
               
            
               
                 SEQ ID NO.: 
                 Name 
                 Sequence (5′-3′) a   
               
               
                   
               
               
                 246 
                 499_NNK_HsCas12a_R499 
                 gaccccgagttctccgccNNKctgacaggcatcaaactg 
               
               
                   
               
               
                 247 
                 500_NNK_HsCas12a_L500 
                 ggaccccgagttctccgccagaNNKacaggcatcaaac 
               
               
                   
               
               
                 248 
                 501_NNK_HsCas12a_T501 
                 cgagttctccgccagactgNNKggcatcaaactggaaatgg 
               
               
                   
               
               
                 249 
                 502_NNK_HsCas12a_G502 
                 gagttctccgccagactgacaNNKatcaaactggaaatggaaccc 
               
               
                   
               
               
                 250 
                 503_NNK_HsCas12a_I503 
                 ctccgccagactgacaggcNNKaaactggaaatggaaccca 
               
               
                   
               
               
                 251 
                 504_NNK_HsCas12a_K504 
                 gccagactgacaggcatcNNKctggaaatggaacccagc 
               
               
                   
               
               
                 252 
                 505_NNK_HsCas12a_L505 
                 ccagactgacaggcatcaaaNNKgaaatggaacccagcctgtc 
               
               
                   
               
               
                 253 
                 506_NNK_HsCas12a_E506 
                 gactgacaggcatcaaactgNNKatggaacccagcctgtcctt 
               
               
                   
               
               
                 254 
                 507_NNK_HsCas12a_M507 
                 ctgacaggcatcaaactggaaNNKgaacccagcctgtccttctac 
               
               
                   
               
               
                 255 
                 508_NNK_HsCas12a_E508 
                 ctgacaggcatcaaactggaaatgNNKcccagcctgtccttc 
               
               
                   
               
               
                 256 
                 509_NNK_HsCas12a_P509 
                 gactgacaggcatcaaactggaaatggaaNNKagcctgtccttctac 
               
               
                   
               
               
                 257 
                 510_NNK_HsCas12a_S510 
                 atcaaactggaaatggaacccNNKctgtccttctacaacaaggcc 
               
               
                   
               
               
                 258 
                 511_NNK_HsCas12a_L511 
                 aaactggaaatggaacccagcNNKtccttctacaacaaggccaga 
               
               
                   
               
               
                 259 
                 512_NNK_HsCas12a_S512 
                 ctggaaatggaacccagcctgNNKttctacaacaaggccagaaac 
               
               
                   
               
               
                 260 
                 513_NNK_HsCas12a_F513 
                 gaaatggaacccagcctgtccNNKtacaacaaggccagaaactac 
               
               
                   
               
               
                 261 
                 514_NNK_HsCas12a_Y514 
                 ggaacccagcctgtccttcNNKaacaaggccagaaactacg 
               
               
                   
               
               
                 262 
                 515_NNK_HsCas12a_N515 
                 cccagcctgtccttctacNNKaaggccagaaactacgcc 
               
               
                   
               
               
                 263 
                 516_NNK_HsCas12a_K516 
                 cagcctgtccttctacaacNNKgccagaaactacgccacca 
               
               
                   
               
               
                 264 
                 517_NNK_HsCas12a_A517 
                 cagcctgtccttctacaacaagNNKagaaactacgccaccaagaaac 
               
               
                   
               
               
                 265 
                 518_NNK_HsCas12a_R518 
                 ctgtccttctacaacaaggccNNKaactacgccaccaagaaaccc 
               
               
                   
               
               
                 266 
                 519_NNK_HsCas12a_N519 
                 tccttctacaacaaggccagaNNKtacgccaccaagaaaccctac 
               
               
                   
               
               
                 267 
                 520_NNK_HsCas12a_Y520 
                 ttctacaacaaggccagaaacNNKgccaccaagaaaccctacagc 
               
               
                   
               
               
                 268 
                 521_NNK_HsCas12a_A521 
                 tacaacaaggccagaaactacNNKaccaagaaaccctacagcgtg 
               
               
                   
               
               
                 269 
                 522_NNK_HsCas12a_T522 
                 caaggccagaaactacgccNNKaagaaaccctacagcgtgg 
               
               
                   
               
               
                 270 
                 523_NNK_HsCas12a_K523 
                 ggccagaaactacgccaccNNKaaaccctacagcgtggaaa 
               
               
                   
               
               
                 271 
                 524_NNK_HsCas12a_K524 
                 ccagaaactacgccaccaagNNKccctacagcgtggaaaagtt 
               
               
                   
               
               
                 272 
                 525_NNK_HsCas12a_P525 
                 ggccagaaactacgccaccaagaaaNNKtacagcgtggaaaagtttaag 
               
               
                   
               
               
                 273 
                 526_NNK_HsCas12a_Y526 
                 aactacgccaccaagaaacccNNKagcgtggaaaagtttaagctg 
               
               
                   
               
               
                 274 
                 527_NNK_HsCas12a_S527 
                 ctacgccaccaagaaaccctacNNKgtggaaaagtttaagctgaactt 
               
               
                   
               
               
                 275 
                 528_NNK_HsCas12a_V528 
                 cgccaccaagaaaccctacagcNNKgaaaagtttaagctgaacttcc 
               
               
                   
               
               
                 276 
                 529_NNK_HsCas12a_E529 
                 caccaagaaaccctacagcgtgNNKaagtttaagctgaacttccaga 
               
               
                   
               
               
                 277 
                 530_NNK_HsCas12a_K530 
                 caagaaaccctacagcgtggaaNNKtttaagctgaacttccagatgc 
               
               
                   
               
               
                 278 
                 531_NNK_HsCas12a_F531 
                 aaaccctacagcgtggaaaagNNKaagctgaacttccagatgccc 
               
               
                   
               
               
                 279 
                 532_NNK_HsCas12a_K532 
                 ccctacagcgtggaaaagtttNNKctgaacttccagatgcccac 
               
               
                   
               
               
                 280 
                 533_NNK_HsCas12a_L533 
                 tacagcgtggaaaagtttaagNNKaacttccagatgcccaccctg 
               
               
                   
               
               
                 281 
                 534_NNK_HsCas12a_N534 
                 gcgtggaaaagtttaagctgNNKttccagatgcccaccctggc 
               
               
                   
               
               
                 282 
                 535_NNK_HsCas12a_F535 
                 cgtggaaaagtttaagctgaacNNKcagatgcccaccctggccag 
               
               
                   
               
               
                 283 
                 536_NNK_HsCas12a_Q536 
                 ggaaaagtttaagctgaacttcNNKatgcccaccctggccagcg 
               
               
                   
               
               
                 284 
                 537_NNK_HsCas12a_M537 
                 ttaagctgaacttccagNNKcccaccctggccagcgg 
               
               
                   
               
               
                 285 
                 538_NNK_HsCas12a_P538 
                 aagctgaacttccagatgNNKaccctggccagcggct 
               
               
                   
               
               
                 286 
                 539_NNK_HsCas12a_T539 
                 gaacttccagatgcccNNKctggccagcggctggg 
               
               
                   
               
               
                 287 
                 540_NNK_HsCas12a_L540 
                 ttccagatgcccaccNNKgccagcggctgggac 
               
               
                   
               
               
                 288 
                 541_NNK_HsCas12a_A541 
                 cagatgcccaccctgNNKagcggctgggacgtg 
               
               
                   
               
               
                 289 
                 542_NNK_HsCas12a_S542 
                 atgcccaccctggccNNKggctgggacgtgaacaa 
               
               
                   
               
               
                 290 
                 543_NNK_HsCas12a_G543 
                 gcccaccctggccagcNNKtgggacgtgaacaaag 
               
               
                   
               
               
                 291 
                 544_NNK_HsCas12a_W544 
                 ccaccctggccagcggcNNKgacgtgaacaaagagaag 
               
               
                   
               
               
                 292 
                 545_NNK_HsCas12a_D545 
                 ccctggccagcggctggNNKgtgaacaaagagaagaac 
               
               
                   
               
               
                 293 
                 546_NNK_HsCas12a_V546 
                 ctggccagcggctgggacNNKaacaaagagaagaacaacg 
               
               
                   
               
               
                 294 
                 547_NNK_HsCas12a_N547 
                 ccagcggctgggacgtgNNKaaagagaagaacaacggc 
               
               
                   
               
               
                 295 
                 548_NNK_HsCas12a_K548 
                 gcggctgggacgtgaacNNKgagaagaacaacggcgc 
               
               
                   
               
               
                 296 
                 549_NNK_HsCas12a_E549 
                 cggctgggacgtgaacaaaNNKaagaacaacggcgccatc 
               
               
                   
               
               
                 297 
                 550_NNK_HsCas12a_K550 
                 ctgggacgtgaacaaagagNNKaacaacggcgccatcctgt 
               
               
                   
               
               
                 298 
                 551_NNK_HsCas12a_N551 
                 gggacgtgaacaaagagaagNNKaacggcgccatcctgttcg 
               
               
                   
               
               
                 299 
                 552_NNK_HsCas12a_N552 
                 gacgtgaacaaagagaagaacNNKggcgccatcctgttcgtgaa 
               
               
                   
               
               
                 300 
                 553_NNK_HsCas12a_G553 
                 cgtgaacaaagagaagaacaacNNKgccatcctgttcgtgaagaacg 
               
               
                   
               
               
                 301 
                 554_NNK_HsCas12a_A554 
                 gaacaaagagaagaacaacggcNNKatcctgttcgtgaagaacggac 
               
               
                   
               
               
                 302 
                 555_NNK_HsCas12a_I555 
                 agagaagaacaacggcgccNNKctgttcgtgaagaacggac 
               
               
                   
               
               
                 303 
                 556_NNK_HsCas12a_L556 
                 gagaagaacaacggcgccatcNNKttcgtgaagaacggactgtac 
               
               
                   
               
               
                 304 
                 557_NNK_HsCas12a_F557 
                 gaacaacggcgccatcctgNNKgtgaagaacggactgtact 
               
               
                   
               
               
                 305 
                 558_NNK_HsCas12a_V558 
                 caacggcgccatcctgttcNNKaagaacggactgtactacc 
               
               
                   
               
               
                 306 
                 559_NNK_HsCas12a_K559 
                 ggcgccatcctgttcgtgNNKaacggactgtactacctg 
               
               
                   
               
               
                 307 
                 560_NNK_HsCas12a_N560 
                 gccatcctgttcgtgaagNNKggactgtactacctgggc 
               
               
                   
               
               
                 308 
                 561_NNK_HsCas12a_G561 
                 gccatcctgttcgtgaagaacNNKctgtactacctgggcatcatg 
               
               
                   
               
               
                 309 
                 562_NNK_HsCas12a_L562 
                 tcctgttcgtgaagaacggaNNKtactacctgggcatcatgcc 
               
               
                   
               
               
                 310 
                 563_NNK_HsCas12a_Y563 
                 ctgttcgtgaagaacggactgNNKtacctgggcatcatgcctaag 
               
               
                   
               
               
                 311 
                 564_NNK_HsCas12a_Y564 
                 cgtgaagaacggactgtacNNKctgggcatcatgcctaagc 
               
               
                   
               
               
                 312 
                 565_NNK_HsCas12a_L565 
                 gtgaagaacggactgtactacNNKggcatcatgcctaagcagaag 
               
               
                   
               
               
                 313 
                 566_NNK_HsCas12a_G566 
                 aagaacggactgtactacctgNNKatcatgcctaagcagaagggc 
               
               
                   
               
               
                 314 
                 567_NNK_HsCas12a_I567 
                 ggactgtactacctgggcNNKatgcctaagcagaagggc 
               
               
                   
               
               
                 315 
                 568_NNK_HsCas12a_M568 
                 gactgtactacctgggcatcNNKcctaagcagaagggcagata 
               
               
                   
               
               
                 316 
                 569_NNK_HsCas12a_P569 
                 ctgtactacctgggcatcatgNNKaagcagaagggcagatacaag 
               
               
                   
               
               
                 317 
                 570_NNK_HsCas12a_K570 
                 ctacctgggcatcatgcctNNKcagaagggcagatacaagg 
               
               
                   
               
               
                 318 
                 571_NNK_HsCas12a_Q571 
                 cctgggcatcatgcctaagNNKaagggcagatacaaggccc 
               
               
                   
               
               
                 319 
                 572_NNK_HsCas12a_K572 
                 ggcatcatgcctaagcagNNKggcagatacaaggccctg 
               
               
                   
               
               
                 320 
                 573_NNK_HsCas12a_G573 
                 ggcatcatgcctaagcagaagNNKagatacaaggccctgtccttt 
               
               
                   
               
               
                 321 
                 574_NNK_HsCas12a_R574 
                 catgcctaagcagaagggcNNKtacaaggccctgtcctttg 
               
               
                   
               
               
                 322 
                 575_NNK_HsCas12a_Y575 
                 gcctaagcagaagggcagaNNKaaggccctgtcctttgagc 
               
               
                   
               
               
                 323 
                 576_NNK_HsCas12a_K576 
                 aagcagaagggcagatacNNKgccctgtcctttgagccc 
               
               
                   
               
               
                 324 
                 577_NNK_HsCas12a_A577 
                 gcagaagggcagatacaagNNKctgtcctttgagcccaccg 
               
               
                   
               
               
                 325 
                 578_NNK_HsCas12a_L578 
                 gaagggcagatacaaggccNNKtcctttgagcccaccgaaa 
               
               
                   
               
               
                 326 
                 579_NNK_HsCas12a_S579 
                 gggcagatacaaggccctgNNKtttgagcccaccgaaaaga 
               
               
                   
               
               
                 327 
                 580_NNK_HsCas12a_F580 
                 agatacaaggccctgtccNNKgagcccaccgaaaagacc 
               
               
                   
               
               
                 328 
                 581_NNK_HsCas12a_E581 
                 ggcagatacaaggccctgtcctttNNKcccaccgaaaagac 
               
               
                   
               
               
                 329 
                 582_NNK_HsCas12a_P582 
                 caaggccctgtcctttgagNNKaccgaaaagaccagcgag 
               
               
                   
               
               
                 330 
                 584_NNK_HsCas12a_E584 
                 ctgtcctttgagcccaccNNKaagaccagcgagggcttt 
               
               
                   
               
               
                 331 
                 584_NNK_HsCas12a_T584 
                 ccctgtcctttgagcccNNKgaaaagaccagcgaggg 
               
               
                   
               
               
                 332 
                 585_NNK_HsCas12a_K585 
                 gtcctttgagcccaccgaaNNKaccagcgagggctttg 
               
               
                   
               
               
                 333 
                 586_NNK_HsCas12a_T586 
                 tgtcctttgagcccaccgaaaagNNKagcgagggctttgac 
               
               
                   
               
               
                 334 
                 587_NNK_HsCas12a_S587 
                 tttgagcccaccgaaaagaccNNKgagggctttgacaagatgtac 
               
               
                   
               
               
                 335 
                 588_NNK_HsCas12a_E588 
                 gagcccaccgaaaagaccagcNNKggctttgacaagatgtactac 
               
               
                   
               
               
                 336 
                 589_NNK_HsCas12a_G589 
                 cccaccgaaaagaccagcgagNNKtttgacaagatgtactacgat 
               
               
                   
               
               
                 337 
                 590_NNK_HsCas12a_F590 
                 accgaaaagaccagcgagggcNNKgacaagatgtactacgattact 
               
               
                   
               
               
                 338 
                 591_NNK_HsCas12a_D591 
                 ccgaaaagaccagcgagggctttNNKaagatgtactacgattacttcc 
               
               
                   
               
               
                 339 
                 592_NNK_HsCas12a_K592 
                 aagaccagcgagggctttgacNNKatgtactacgattacttcccc 
               
               
                   
               
               
                 340 
                 593_NNK_HsCas12a_M593 
                 ccagcgagggctttgacaagNNKtactacgattacttccccga 
               
               
                   
               
               
                 341 
                 594_NNK_HsCas12a_Y594 
                 gcgagggctttgacaagatgNNKtacgattacttccccgacgc 
               
               
                   
               
               
                 342 
                 595_NNK_HsCas12a_Y595 
                 gggctttgacaagatgtacNNKgattacttccccgacgccg 
               
               
                   
               
               
                 343 
                 596_NNK_HsCas12a_D596 
                 ggctttgacaagatgtactacNNKtacttccccgacgccgccaa 
               
               
                   
               
               
                 344 
                 597_NNK_HsCas12a_Y597 
                 agggctttgacaagatgtactacgatNNKttccccgacgccgc 
               
               
                   
               
               
                 345 
                 598_NNK_HsCas12a_F598 
                 gctttgacaagatgtactacgattacNNKcccgacgccgccaaga 
               
               
                   
               
               
                 346 
                 599_NNK_HsCas12a_P599 
                 tttgacaagatgtactacgattacttcNNKgacgccgccaagatgatc 
               
               
                   
               
               
                 347 
                 600_NNK_HsCas12a_D600 
                 gtactacgattacttccccNNKgccgccaagatgatcccca 
               
               
                   
               
               
                 348 
                 601_NNK_HsCas12a_A601 
                 actacgattacttccccgacNNKgccaagatgatccccaagtg 
               
               
                   
               
               
                 349 
                 602_NNK_HsCas12a_A602 
                 cgattacttccccgacgccNNKaagatgatccccaagtgca 
               
               
                   
               
               
                 350 
                 603_NNK_HsCas12a_K603 
                 cttccccgacgccgccNNKatgatccccaagtgca 
               
               
                   
               
               
                 351 
                 604_NNK_HsCas12a_M604 
                 cccgacgccgccaagNNKatccccaagtgcagc 
               
               
                   
               
               
                 352 
                 605_NNK_HsCas12a_I605 
                 cgacgccgccaagatgNNKcccaagtgcagcaccc 
               
               
                   
               
               
                 353 
                 606_NNK_HsCas12a_P606 
                 gacgccgccaagatgatcNNKaagtgcagcacccagctg 
               
               
                   
               
               
                 354 
                 607_NNK_HsCas12a_K607 
                 ccgccaagatgatccccNNKtgcagcacccagctgaa 
               
               
                   
               
               
                 355 
                 608_NNK_HsCas12a_C608 
                 gccaagatgatccccaagNNKagcacccagctgaaggcc 
               
               
                   
               
               
                 356 
                 609_NNK_HsCas12a_S609 
                 aagatgatccccaagtgcNNKacccagctgaaggccgtg 
               
               
                   
               
               
                 357 
                 610_NNK_HsCas12a_T610 
                 tgatccccaagtgcagcNNKcagctgaaggccgtgac 
               
               
                   
               
               
                 358 
                 611_NNK_HsCas12a_Q611 
                 ccccaagtgcagcaccNNKctgaaggccgtgaccg 
               
               
                   
               
               
                 359 
                 613_NNK_HsCas12a_K613 
                 tgcagcacccagctgNNKgccgtgaccgcccac 
               
               
                   
               
               
                 360 
                 613_NNK_HsCas12a_L613 
                 caagtgcagcacccagNNKaaggccgtgaccgccc 
               
               
                   
               
               
                 361 
                 614_NNK_HsCas12a_A614 
                 gcagcacccagctgaagNNKgtgaccgcccactttca 
               
               
                   
               
               
                 362 
                 615_NNK_HsCas12a_V615 
                 gcacccagctgaaggccNNKaccgcccactttcagac 
               
               
                   
               
               
                 363 
                 616_NNK_HsCas12a_T616 
                 ccagctgaaggccgtgNNKgcccactttcagaccc 
               
               
                   
               
               
                 364 
                 617_NNK_HsCas12a_A617 
                 cagctgaaggccgtgaccNNKcactttcagacccacacc 
               
               
                   
               
               
                 365 
                 618_NNK_HsCas12a_H618 
                 tgaaggccgtgaccgccNNKtttcagacccacaccac 
               
               
                   
               
               
                 366 
                 619_NNK_HsCas12a_F619 
                 gccgtgaccgcccacNNKcagacccacaccacc 
               
               
                   
               
               
                 367 
                 620_NNK_HsCas12a_Q620 
                 aaggccgtgaccgcccactttNNKacccacaccacc 
               
               
                   
               
               
                 368 
                 621_NNK_HsCas12a_T621 
                 gaccgcccactttcagNNKcacaccacccccatcc 
               
               
                   
               
               
                 369 
                 622_NNK_HsCas12a_H622 
                 cgcccactttcagaccNNKaccacccccatcctgc 
               
               
                   
               
               
                 370 
                 623_NNK_HsCas12a_T623 
                 cccactttcagacccacNNKacccccatcctgctgag 
               
               
                   
               
               
                 371 
                 624_NNK_HsCas12a_T624 
                 cactttcagacccacaccNNKcccatcctgctgagcaac 
               
               
                   
               
               
                 372 
                 625_NNK_HsCas12a_P625 
                 cactttcagacccacaccaccNNKatcctgctgagcaacaacttc 
               
               
                   
               
               
                 373 
                 626_NNK_HsCas12a_I626 
                 cagacccacaccacccccNNKctgctgagcaacaacttc 
               
               
                   
               
               
                 374 
                 627_NNK_HsCas12a_L627 
                 gacccacaccacccccatcNNKctgagcaacaacttcatcg 
               
               
                   
               
               
                 375 
                 628_NNK_HsCas12a_L628 
                 ccacaccacccccatcctgNNKagcaacaacttcatcgagc 
               
               
                   
               
               
                 376 
                 629_NNK_HsCas12a_S629 
                 accacccccatcctgctgNNKaacaacttcatcgagccc 
               
               
                   
               
               
                 377 
                 630_NNK_HsCas12a_N630 
                 cccccatcctgctgagcNNKaacttcatcgagcccct 
               
               
                   
               
               
                 378 
                 631_NNK_HsCas12a_N631 
                 cccatcctgctgagcaacNNKttcatcgagcccctggaa 
               
               
                   
               
               
                 379 
                 632_NNK_HsCas12a_F632 
                 ccatcctgctgagcaacaacNNKatcgagcccctggaaatcac 
               
               
                   
               
               
                 380 
                 633_NNK_HsCas12a_I633 
                 cctgctgagcaacaacttcNNKgagcccctggaaatcacca 
               
               
                   
               
               
                 381 
                 634_NNK_HsCas12a_E634 
                 cctgctgagcaacaacttcatcNNKcccctggaaatcaccaaagag 
               
               
                   
               
               
                 382 
                 635_NNK_HsCas12a_P635 
                 gctgagcaacaacttcatcgagNNKctggaaatcaccaaagagatct 
               
               
                   
               
               
                 383 
                 636_NNK_HsCas12a_L636 
                 gagcaacaacttcatcgagcccNNKgaaatcaccaaagagatctacg 
               
               
                   
               
               
                 384 
                 637_NNK_HsCas12a_E637 
                 aacaacttcatcgagcccctgNNKatcaccaaagagatctacgac 
               
               
                   
               
               
                 385 
                 638_NNK_HsCas12a_I638 
                 aacaacttcatcgagcccctggaaNNKaccaaagagatctacgacc 
               
               
                   
               
               
                 386 
                 639_NNK_HsCas12a_T639 
                 ttcatcgagcccctggaaatcNNKaaagagatctacgacctgaac 
               
               
                   
               
               
                 387 
                 640_NNK_HsCas12a_K640 
                 cgagcccctggaaatcaccNNKgagatctacgacctgaaca 
               
               
                   
               
               
                 388 
                 840_NNK_HsCas12a_D840 
                 ctgagccacgacctgtccNNKgaagctagagcactgctg 
               
               
                   
               
               
                 389 
                 841_NNK_HsCas12a_E841 
                 ccacgacctgtccgacNNKgctagagcactgctgc 
               
               
                   
               
               
                 390 
                 842_NNK_HsCas12a_A842 
                 ccacgacctgtccgacgaaNNKagagcactgctgccc 
               
               
                   
               
               
                 391 
                 843_NNK_HsCas12a_R843 
                 gacctgtccgacgaagctNNKgcactgctgcccaacg 
               
               
                   
               
               
                 392 
                 844_NNK_HsCas12a_A844 
                 ctgtccgacgaagctagaNNKctgctgcccaacgtgatc 
               
               
                   
               
               
                 393 
                 845_NNK_HsCas12a_L845 
                 gtccgacgaagctagagcaNNKctgcccaacgtgatcacaa 
               
               
                   
               
               
                 394 
                 846_NNK_HsCas12a_L846 
                 ccgacgaagctagagcactgNNKcccaacgtgatcacaaaaga 
               
               
                   
               
               
                 395 
                 847_NNK_HsCas12a_P847 
                 gacgaagctagagcactgctgNNKaacgtgatcacaaaagaggtg 
               
               
                   
               
               
                 396 
                 848_NNK_HsCas12a_N848 
                 aagctagagcactgctgcccNNKgtgatcacaaaagaggtgtc 
               
               
                   
               
               
                 397 
                 849_NNK_HsCas12a_V849 
                 ctagagcactgctgcccaacNNKatcacaaaagaggtgtccca 
               
               
                   
               
               
                 398 
                 850_NNK_HsCas12a_I850 
                 gcactgctgcccaacgtgNNKacaaaagaggtgtcccac 
               
               
                   
               
               
                 399 
                 851_NNK_HsCas12a_T851 
                 ctgctgcccaacgtgatcNNKaaagaggtgtcccacgag 
               
               
                   
               
               
                 400 
                 852_NNK_HsCas12a_K852 
                 ctgcccaacgtgatcacaNNKgaggtgtcccacgagatc 
               
               
                   
               
               
                 401 
                 853_NNK_HsCas12a_E853 
                 cactgctgcccaacgtgatcacaaaaNNKgtgtcccacgagat 
               
               
                   
               
               
                 402 
                 854_NNK_HsCas12a_V854 
                 gcccaacgtgatcacaaaagagNNKtcccacgagatcatcaaggac 
               
               
                   
               
               
                 403 
                 855_NNK_HsCas12a_S855 
                 aacgtgatcacaaaagaggtgNNKcacgagatcatcaaggaccgg 
               
               
                   
               
               
                 404 
                 856_NNK_HsCas12a_H856 
                 tgatcacaaaagaggtgtccNNKgagatcatcaaggaccggcg 
               
               
                   
               
               
                 405 
                 857_NNK_HsCas12a_E857 
                 cacaaaagaggtgtcccacNNKatcatcaaggaccggcggt 
               
               
                   
               
               
                 406 
                 858_NNK_HsCas12a_I858 
                 caaaagaggtgtcccacgagNNKatcaaggaccggcggtttac 
               
               
                   
               
               
                 407 
                 859_NNK_HsCas12a_I859 
                 gaggtgtcccacgagatcNNKaaggaccggcggtttacc 
               
               
                   
               
               
                 408 
                 860_NNK_HsCas12a_K860 
                 gtgtcccacgagatcatcNNKgaccggcggtttacctc 
               
               
                   
               
               
                 409 
                 861_NNK_HsCas12a_D861 
                 gtgtcccacgagatcatcaagNNKcggcggtttacctcc 
               
               
                   
               
               
                 410 
                 862_NNK_HsCas12a_R862 
                 tcccacgagatcatcaaggacNNKcggtttacctccgataagttc 
               
               
                   
               
               
                 411 
                 863_NNK_HsCas12a_R863 
                 cacgagatcatcaaggaccggNNKtttacctccgataagttcttc 
               
               
                   
               
               
                 412 
                 864_NNK_HsCas12a_F864 
                 gagatcatcaaggaccggcggNNKacctccgataagttcttcttc 
               
               
                   
               
               
                 413 
                 865_NNK_HsCas12a_T865 
                 cgagatcatcaaggaccggcggtttNNKtccgataagttcttcttc 
               
               
                   
               
               
                 414 
                 866_NNK_HsCas12a_S866 
                 atcaaggaccggcggtttaccNNKgataagttcttcttccacgtg 
               
               
                   
               
               
                 415 
                 867_NNK_HsCas12a_D867 
                 ggaccggcggtttacctccNNKaagttcttcttccacgtgc 
               
               
                   
               
               
                 416 
                 868_NNK_HsCas12a_K868 
                 ccggcggtttacctccgatNNKttcttcttccacgtgccc 
               
               
                   
               
               
                 417 
                 869_NNK_HsCas12a_F869 
                 ggcggtttacctccgataagNNKttcttccacgtgcccatcac 
               
               
                   
               
               
                 418 
                 870_NNK_HsCas12a_F870 
                 ggtttacctccgataagttcNNKttccacgtgcccatcaccct 
               
               
                   
               
               
                 419 
                 871_NNK_HsCas12a_F871 
                 tttacctccgataagttcttcNNKcacgtgcccatcaccctgaac 
               
               
                   
               
               
                 420 
                 872_NNK_HsCas12a_H872 
                 acctccgataagttcttcttcNNKgtgcccatcaccctgaactac 
               
               
                   
               
               
                 421 
                 873_NNK_HsCas12a_V873 
                 tccgataagttcttcttccacNNKcccatcaccctgaactaccag 
               
               
                   
               
               
                 422 
                 874_NNK_HsCas12a_P874 
                 gataagttcttcttccacgtgNNKatcaccctgaactaccaggcc 
               
               
                   
               
               
                 423 
                 875_NNK_HsCas12a_I875 
                 ttcttcttccacgtgcccNNKaccctgaactaccaggcc 
               
               
                   
               
               
                 424 
                 876_NNK_HsCas12a_T876 
                 tcttccacgtgcccatcNNKctgaactaccaggccgc 
               
               
                   
               
               
                 425 
                 877_NNK_HsCas12a_L877 
                 ccacgtgcccatcaccNNKaactaccaggccgcca 
               
               
                   
               
               
                 426 
                 878_NNK_HsCas12a_N878 
                 cgtgcccatcaccctgNNKtaccaggccgccaaca 
               
               
                   
               
               
                 427 
                 879_NNK_HsCas12a_Y879 
                 gcccatcaccctgaacNNKcaggccgccaacagcc 
               
               
                   
               
               
                 428 
                 880_NNK_HsCas12a_Q880 
                 ccatcaccctgaactacNNKgccgccaacagcccca 
               
               
                   
               
               
                 429 
                 881_NNK_HsCas12a_A881 
                 atcaccctgaactaccagNNKgccaacagccccagcaag 
               
               
                   
               
               
                 430 
                 882_NNK_HsCas12a_A882 
                 accctgaactaccaggccNNKaacagccccagcaagttc 
               
               
                   
               
               
                 431 
                 883_NNK_HsCas12a_N883 
                 ctgaactaccaggccgccNNKagccccagcaagttcaac 
               
               
                   
               
               
                 432 
                 884_NNK_HsCas12a_S884 
                 aactaccaggccgccaacNNKcccagcaagttcaaccag 
               
               
                   
               
               
                 433 
                 885_NNK_HsCas12a_P885 
                 ctaccaggccgccaacagcNNKagcaagttcaaccagagag 
               
               
                   
               
               
                 434 
                 886_NNK_HsCas12a_S886 
                 caggccgccaacagccccNNKaagttcaaccagagagtg 
               
               
                   
               
               
                 435 
                 887_NNK_HsCas12a_K887 
                 gccgccaacagccccagcNNKttcaaccagagagtgaac 
               
               
                   
               
               
                 436 
                 888_NNK_HsCas12a_F888 
                 gccaacagccccagcaagNNKaaccagagagtgaacgcc 
               
               
                   
               
               
                 437 
                 889_NNK_HsCas12a_N889 
                 caacagccccagcaagttcNNKcagagagtgaacgcctacc 
               
               
                   
               
               
                 438 
                 890_NNK_HsCas12a_Q890 
                 cagccccagcaagttcaacNNKagagtgaacgcctacctga 
               
               
                   
               
               
                 439 
                 891_NNK_HsCas12a_R891 
                 ccccagcaagttcaaccagNNKgtgaacgcctacctgaaag 
               
               
                   
               
               
                 440 
                 892_NNK_HsCas12a_V892 
                 cccagcaagttcaaccagagaNNKaacgcctacctgaaagagcac 
               
               
                   
               
               
                 441 
                 893_NNK_HsCas12a_N893 
                 gcaagttcaaccagagagtgNNKgcctacctgaaagagcaccc 
               
               
                   
               
               
                 442 
                 894_NNK_HsCas12a_A894 
                 aagttcaaccagagagtgaacNNKtacctgaaagagcaccccgag 
               
               
                   
               
               
                 443 
                 895_NNK_HsCas12a_Y895 
                 aaccagagagtgaacgccNNKctgaaagagcaccccgag 
               
               
                   
               
               
                 444 
                 896_NNK_HsCas12a_L896 
                 ccagagagtgaacgcctacNNKaaagagcaccccgagacac 
               
               
                   
               
               
                 445 
                 897_NNK_HsCas12a_K897 
                 gagtgaacgcctacctgNNKgagcaccccgagacacc 
               
               
                   
               
               
                 446 
                 898_NNK_HsCas12a_E898 
                 agagagtgaacgcctacctgaaaNNKcaccccgagacacc 
               
               
                   
               
               
                 447 
                 899_NNK_HsCas12a_H899 
                 gaacgcctacctgaaagagNNKcccgagacacccatcattg 
               
               
                   
               
               
                 448 
                 900_NNK_HsCas12a_P900 
                 cgcctacctgaaagagcacNNKgagacacccatcattggca 
               
               
                   
               
               
                 449 
                 901_NNK_HsCas12a_E901 
                 ctacctgaaagagcaccccNNKacacccatcattggcatcg 
               
               
                   
               
               
                 450 
                 902_NNK_HsCas12a_T902 
                 ctgaaagagcaccccgagNNKcccatcattggcatcgac 
               
               
                   
               
               
                 451 
                 903_NNK_HsCas12a_P903 
                 tgaaagagcaccccgagacaNNKatcattggcatcgacagagg 
               
               
                   
               
               
                 452 
                 904_NNK_HsCas12a_I904 
                 agcaccccgagacacccNNKattggcatcgacagagg 
               
               
                   
               
               
                 453 
                 905_NNK_HsCas12a_I905 
                 ccccgagacacccatcNNKggcatcgacagaggcg 
               
               
                   
               
               
                 454 
                 906_NNK_HsCas12a_G906 
                 gagcaccccgagacacccatcattNNKatcgacagaggcg 
               
               
                   
               
               
                 455 
                 907_NNK_HsCas12a_I907 
                 gagacacccatcattggcNNKgacagaggcgagcggaac 
               
               
                   
               
               
                 456 
                 908_NNK_HsCas12a_D908 
                 acacccatcattggcatcNNKagaggcgagcggaacctg 
               
               
                   
               
               
                 457 
                 909_NNK_HsCas12a_R909 
                 cccatcattggcatcgacNNKggcgagcggaacctgatc 
               
               
                   
               
               
                 458 
                 910_NNK_HsCas12a_G910 
                 cccatcattggcatcgacagaNNKgagcggaacctgatctacatc 
               
               
                   
               
               
                 459 
                 911_NNK_HsCas12a_E911 
                 tcattggcatcgacagaggcNNKcggaacctgatctacatcac 
               
               
                   
               
               
                 460 
                 912_NNK_HsCas12a_R912 
                 tggcatcgacagaggcgagNNKaacctgatctacatcaccg 
               
               
                   
               
               
                 461 
                 913_NNK_HsCas12a_N913 
                 atcgacagaggcgagcggNNKctgatctacatcaccgtg 
               
               
                   
               
               
                   a For “NNK”, N refers to A, C, T or G; K refers to G or T. 
               
            
           
         
       
     
     With respect to Table 4, the reference (i.e., wild-type) polypeptide sequence is SEQ ID NO.: 462 upon which these mutants are based by comparison. Polynucleotides codon-optimized for expression in  E. coli  and human cells that encode SEQ ID NO.:462 are SEQ ID NOs.: 463 and 464, respectively. The same mutations were introduced as well into M537R/F870L-AsCas12a background. The corresponding reference polypeptide sequence for the M537R/F870L-Cas12a is SEQ ID NO.: 465 (the altered amino acids are underlined). Polynucleotides codon-optimized for expression in  E. coli  and human cells that encode SEQ ID NO.:465 are SEQ ID NOs.: 466 and 467, respectively (the altered codons are underlined). 
     
       
         
           
               
            
               
                 SEQ ID NO.: 462 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRN 
               
               
                   
               
               
                 SEQ ID NO.: 463 
               
               
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCT 
               
               
                   
               
               
                 GCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAAC 
               
               
                   
               
               
                 AGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTG 
               
               
                   
               
               
                 AAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATC 
               
               
                   
               
               
                 GCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCA 
               
               
                   
               
               
                 ACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCT 
               
               
                   
               
               
                 GACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACC 
               
               
                   
               
               
                 ACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCAC 
               
               
                   
               
               
                 CTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAG 
               
               
                   
               
               
                 ATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAG 
               
               
                   
               
               
                 CCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTA 
               
               
                   
               
               
                 GCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTG 
               
               
                   
               
               
                 ACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGG 
               
               
                   
               
               
                 CCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCAT 
               
               
                   
               
               
                 CGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAG 
               
               
                   
               
               
                 CTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAA 
               
               
                   
               
               
                 GCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAG 
               
               
                   
               
               
                 CCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATA 
               
               
                   
               
               
                 CCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGA 
               
               
                   
               
               
                 TATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAG 
               
               
                   
               
               
                 CATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGT 
               
               
                   
               
               
                 TTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTG 
               
               
                   
               
               
                 ACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGC 
               
               
                   
               
               
                 CCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                 ACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAA 
               
               
                   
               
               
                 AACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTAT 
               
               
                   
               
               
                 TATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGG 
               
               
                   
               
               
                 AAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGC 
               
               
                   
               
               
                 ACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTG 
               
               
                   
               
               
                 AACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAA 
               
               
                   
               
               
                 GAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTC 
               
               
                   
               
               
                 TGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCG 
               
               
                   
               
               
                 AGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTT 
               
               
                   
               
               
                 GCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGG 
               
               
                   
               
               
                 TCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTC 
               
               
                   
               
               
                 AGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCC 
               
               
                   
               
               
                 GATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTC 
               
               
                   
               
               
                 TGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATT 
               
               
                   
               
               
                 ACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                 CAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATA 
               
               
                   
               
               
                 GCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCA 
               
               
                   
               
               
                 GAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATAT 
               
               
                   
               
               
                 CACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAA 
               
               
                   
               
               
                 CGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCT 
               
               
                   
               
               
                 GAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGA 
               
               
                   
               
               
                 TTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACC 
               
               
                   
               
               
                 AGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTG 
               
               
                   
               
               
                 TTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGT 
               
               
                   
               
               
                 TTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTT 
               
               
                   
               
               
                 TAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAA 
               
               
                   
               
               
                 GGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCA 
               
               
                   
               
               
                 TCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCG 
               
               
                   
               
               
                 CACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGC 
               
               
                   
               
               
                 ACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTG 
               
               
                   
               
               
                 AAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGAT 
               
               
                   
               
               
                 AGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAA 
               
               
                   
               
               
                 GCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCA 
               
               
                   
               
               
                 TATATCCAAGAACTGCGTAAC 
               
               
                   
               
               
                 SEQ ID NO.: 464 
               
               
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCT 
               
               
                   
               
               
                 GCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAAC 
               
               
                   
               
               
                 AGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTG 
               
               
                   
               
               
                 AAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATC 
               
               
                   
               
               
                 GCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCA 
               
               
                   
               
               
                 ACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCT 
               
               
                   
               
               
                 GACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACC 
               
               
                   
               
               
                 ACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCAC 
               
               
                   
               
               
                 CTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAG 
               
               
                   
               
               
                 ATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAG 
               
               
                   
               
               
                 CCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTA 
               
               
                   
               
               
                 GCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTG 
               
               
                   
               
               
                 ACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGG 
               
               
                   
               
               
                 CCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCAT 
               
               
                   
               
               
                 CGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAG 
               
               
                   
               
               
                 CTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAA 
               
               
                   
               
               
                 GCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAG 
               
               
                   
               
               
                 CCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATA 
               
               
                   
               
               
                 CCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGA 
               
               
                   
               
               
                 TATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAG 
               
               
                   
               
               
                 CATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGT 
               
               
                   
               
               
                 TTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTG 
               
               
                   
               
               
                 ACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGC 
               
               
                   
               
               
                 CCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                 ACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAA 
               
               
                   
               
               
                 AACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTAT 
               
               
                   
               
               
                 TATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGG 
               
               
                   
               
               
                 AAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGC 
               
               
                   
               
               
                 ACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTG 
               
               
                   
               
               
                 AACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAA 
               
               
                   
               
               
                 GAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTC 
               
               
                   
               
               
                 TGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCG 
               
               
                   
               
               
                 AGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTT 
               
               
                   
               
               
                 GCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGG 
               
               
                   
               
               
                 TCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTC 
               
               
                   
               
               
                 AGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCC 
               
               
                   
               
               
                 GATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTC 
               
               
                   
               
               
                 TGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATT 
               
               
                   
               
               
                 ACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                 CAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATA 
               
               
                   
               
               
                 GCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCA 
               
               
                   
               
               
                 GAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATAT 
               
               
                   
               
               
                 CACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAA 
               
               
                   
               
               
                 CGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCT 
               
               
                   
               
               
                 GAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGA 
               
               
                   
               
               
                 TTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACC 
               
               
                   
               
               
                 AGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTG 
               
               
                   
               
               
                 TTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGT 
               
               
                   
               
               
                 TTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTT 
               
               
                   
               
               
                 TAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAA 
               
               
                   
               
               
                 GGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCA 
               
               
                   
               
               
                 TCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCG 
               
               
                   
               
               
                 CACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGC 
               
               
                   
               
               
                 ACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTG 
               
               
                   
               
               
                 AAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGAT 
               
               
                   
               
               
                 AGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAA 
               
               
                   
               
               
                 GCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCA 
               
               
                   
               
               
                 TATATCCAAGAACTGCGTAAC 
               
               
                   
               
               
                 SEQ ID NO.: 465 
               
               
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEEDKARNDHYKEL 
               
               
                   
               
               
                 KPIIDRIYKTYADQCLQLVQLDWENLSAAIDSYRKEKTEETRNALIEEQA 
               
               
                   
               
               
                 TYRNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQLGTVT 
               
               
                   
               
               
                 TTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDISTAIPHRIVQDNFPK 
               
               
                   
               
               
                 FKENCHIFTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPFYNQLL 
               
               
                   
               
               
                 TQTQIDLYNQLLGGISREAGTEKIKGLNEVLNLAIQKNDETAHIIASLPH 
               
               
                   
               
               
                 RFIPLFKQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTLRNALYERRISELTGK 
               
               
                   
               
               
                 ITKSAKEKVQRSLKHEDINLQEIISAAGKELSEAFKQKTSEILSHAHAAL 
               
               
                   
               
               
                 DQPLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARL 
               
               
                   
               
               
                 TGIKLEMEPSLSFYNKARNYATKKPYSVEKFKLNFQ R PTLASGWDVNKEK 
               
               
                   
               
               
                 NNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYYDYFPD 
               
               
                   
               
               
                 AAKMIPKCSTQLKAVTAHFQTHTTPILLSNNFIEPLEITKEIYDLNNPEK 
               
               
                   
               
               
                 EPKKFQTAYAKKTGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIYNKDF 
               
               
                   
               
               
                 AKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAELFYRPKSRMKRMAH 
               
               
                   
               
               
                 RLGEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSDEARALLPNVI 
               
               
                   
               
               
                 TKEVSHEIIKDRRFTSDKF L FHVPITLNYQAANSPSKFNQRVNAYLKEHP 
               
               
                   
               
               
                 ETPIIGIDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNREKE 
               
               
                   
               
               
                 RVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQAVVVLENLNFGFK 
               
               
                   
               
               
                 SKRTGIAEKAVYQQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEG 
               
               
                   
               
               
                 FDFLHYDVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAK 
               
               
                   
               
               
                 GTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLEEKGIVFRDGSNIL 
               
               
                   
               
               
                 PKLLENDDSHAIDTMVALIRSVLQMRNSNAATGEDYINSPVRDLNGVCFD 
               
               
                   
               
               
                 SRFQNPEWPMDADANGAYHIALKGQLLLNHLKESKDLKLQNGISNQDWLA 
               
               
                   
               
               
                 YIQELRN 
               
               
                   
               
               
                 SEQ ID NO.: 466 
               
               
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCT 
               
               
                   
               
               
                 GCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAAC 
               
               
                   
               
               
                 AGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTG 
               
               
                   
               
               
                 AAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATC 
               
               
                   
               
               
                 GCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCA 
               
               
                   
               
               
                 ACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCT 
               
               
                   
               
               
                 GACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACC 
               
               
                   
               
               
                 ACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCAC 
               
               
                   
               
               
                 CTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAG 
               
               
                   
               
               
                 ATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAG 
               
               
                   
               
               
                 CCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTA 
               
               
                   
               
               
                 GCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTG 
               
               
                   
               
               
                 ACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGG 
               
               
                   
               
               
                 CCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCAT 
               
               
                   
               
               
                 CGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAG 
               
               
                   
               
               
                 CTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAA 
               
               
                   
               
               
                 GCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAG 
               
               
                   
               
               
                 CCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATA 
               
               
                   
               
               
                 CCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGA 
               
               
                   
               
               
                 TATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAG 
               
               
                   
               
               
                 CATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGT 
               
               
                   
               
               
                 TTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTG 
               
               
                   
               
               
                 ACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGC 
               
               
                   
               
               
                 CCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                 ACTTTCAG CGT CCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAA 
               
               
                   
               
               
                 AACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTAT 
               
               
                   
               
               
                 TATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGG 
               
               
                   
               
               
                 AAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGC 
               
               
                   
               
               
                 ACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTG 
               
               
                   
               
               
                 AACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAA 
               
               
                   
               
               
                 GAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTC 
               
               
                   
               
               
                 TGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCG 
               
               
                   
               
               
                 AGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTT 
               
               
                   
               
               
                 GCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGG 
               
               
                   
               
               
                 TCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTC 
               
               
                   
               
               
                 AGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCC 
               
               
                   
               
               
                 GATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTC 
               
               
                   
               
               
                 TGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATT 
               
               
                   
               
               
                 ACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                 CAAATTC CTG TTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATA 
               
               
                   
               
               
                 GCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCA 
               
               
                   
               
               
                 GAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATAT 
               
               
                   
               
               
                 CACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAA 
               
               
                   
               
               
                 CGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCT 
               
               
                   
               
               
                 GAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGA 
               
               
                   
               
               
                 TTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACC 
               
               
                   
               
               
                 AGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTG 
               
               
                   
               
               
                 TTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGT 
               
               
                   
               
               
                 TTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTT 
               
               
                   
               
               
                 TAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAA 
               
               
                   
               
               
                 GGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCA 
               
               
                   
               
               
                 TCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCG 
               
               
                   
               
               
                 CACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGC 
               
               
                   
               
               
                 ACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTG 
               
               
                   
               
               
                 AAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGAT 
               
               
                   
               
               
                 AGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAA 
               
               
                   
               
               
                 GCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCA 
               
               
                   
               
               
                 TATATCCAAGAACTGCGTAAC 
               
               
                   
               
               
                 SEQ ID NO.: 467 
               
               
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCAAAACCCT 
               
               
                   
               
               
                 GCGTTTTGAACTGATTCCGCAGGGTAAAACCCTGAAACATATTCAAGAAC 
               
               
                   
               
               
                 AGGGCTTCATCGAAGAGGATAAAGCACGTAACGATCACTACAAAGAACTG 
               
               
                   
               
               
                 AAACCGATTATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGATAGTTATC 
               
               
                   
               
               
                 GCAAAGAAAAAACCGAAGAAACCCGTAATGCACTGATTGAAGAACAGGCA 
               
               
                   
               
               
                 ACCTATCGTAATGCCATCCATGATTATTTCATTGGTCGTACCGATAATCT 
               
               
                   
               
               
                 GACCGATGCAATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCACCGTTACC 
               
               
                   
               
               
                 ACCACCGAACATGAAAATGCACTGCTGCGTAGCTTTGATAAATTCACCAC 
               
               
                   
               
               
                 CTATTTCAGCGGCTTTTATGAGAATCGCAAAAACGTGTTTAGCGCAGAAG 
               
               
                   
               
               
                 ATATTAGCACCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAGTTCCGAG 
               
               
                   
               
               
                 CCTGCGTGAACATTTTGAAAACGTTAAAAAAGCCATCGGCATCTTTGTTA 
               
               
                   
               
               
                 GCACCAGCATTGAAGAAGTTTTTAGCTTCCCGTTTTACAATCAGCTGCTG 
               
               
                   
               
               
                 ACCCAGACCCAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTGAATCTGG 
               
               
                   
               
               
                 CCATTCAGAAAAATGATGAAACCGCACATATTATTGCAAGCCTGCCGCAT 
               
               
                   
               
               
                 CGTTTTATTCCGCTGTTCAAACAAATTCTGAGCGATCGTAATACCCTGAG 
               
               
                   
               
               
                 CTTTATTCTGGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAACTGCCGAA 
               
               
                   
               
               
                 GCACTGTTTAACGAACTGAATAGCATTGATCTGACCCACATCTTTATCAG 
               
               
                   
               
               
                 CCACAAAAAACTGGAAACCATTTCAAGCGCACTGTGTGATCATTGGGATA 
               
               
                   
               
               
                 CCCTGCGTAATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAACATGAGGA 
               
               
                   
               
               
                 TATTAATCTGCAAGAGATTATTAGCGCAGCCGGTAAAGAACTGTCAGAAG 
               
               
                   
               
               
                 CATTTAAACAGAAAACCAGCGAAATTCTGTCACATGCACATGCAGCACTG 
               
               
                   
               
               
                 GATCAGCCGCTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTGGACTGGT 
               
               
                   
               
               
                 TTGCAGTTGATGAAAGCAATGAAGTTGATCCGGAATTTAGCGCACGTCTG 
               
               
                   
               
               
                 ACCGGCATTAAACTGGAAATGGAACCGAGCCTGAGCTTTTATAACAAAGC 
               
               
                   
               
               
                 CCGTAATTATGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                 ACTTTCAG CGT CCGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAA 
               
               
                   
               
               
                 AACAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTATCTGGGTAT 
               
               
                   
               
               
                 TATGCCGAAACAGAAAGGTCGTTATAAAGCGCTGAGCTTTGAACCGACGG 
               
               
                   
               
               
                 AAAAAACCAGTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAGTTACCGC 
               
               
                   
               
               
                 ACATTTTCAGACCCATACCACCCCGATTCTGCTGAGCAATAACTTTATTG 
               
               
                   
               
               
                 AACCGCTGGAAATCACCAAAGAGATCTACGATCTGAATAACCCGGAAAAA 
               
               
                   
               
               
                 GAGCCGAAAAAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGTGATTTTC 
               
               
                   
               
               
                 TGAGCAAATACACCAAAACCACCAGTATCGATCTGAGCAGCCTGCGTCCG 
               
               
                   
               
               
                 AGCAGCCAGTATAAAGATCTGGGCGAATATTATGCAGAACTGAATCCGCT 
               
               
                   
               
               
                 GCTGTATCATATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTT 
               
               
                   
               
               
                 GCCAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTATTGGACCGG 
               
               
                   
               
               
                 TCTGTTTAGCCCTGAAAATCTGGCAAAAACCTCGATTAAACTGAATGGTC 
               
               
                   
               
               
                 AGGCGGAACTGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCC 
               
               
                   
               
               
                 GATCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAACCATCGTC 
               
               
                   
               
               
                 TGAGCCATGATCTGAGTGATGAAGCACGTGCCCTGCTGCCGAATGTTATT 
               
               
                   
               
               
                 ACCAAAGAAGTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                 CAAATTC CTG TTTCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATA 
               
               
                   
               
               
                 GCCCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAGAACATCCA 
               
               
                   
               
               
                 GAAACGCCGATTATTGGTATTGATCGTGGTGAACGTAACCTGATTTATAT 
               
               
                   
               
               
                 CACCGTTATTGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAA 
               
               
                   
               
               
                 CGTGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATTAAAGACCT 
               
               
                   
               
               
                 GAAACAGGGTTATCTGAGCCAGGTTATTCATGAAATTGTGGATCTGATGA 
               
               
                   
               
               
                 TTCACTATCAGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGTTCGAGAA 
               
               
                   
               
               
                 AATGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTATCCGGCTG 
               
               
                   
               
               
                 AAAAAGTTGGTGGTGTTCTGAATCCGTATCAGCTGACCGATCAGTTTACC 
               
               
                   
               
               
                 AGCTTTGCAAAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGATCCGTTTG 
               
               
                   
               
               
                 TTTGGAAAACCATCAAAAACCATGAAAGCCGCAAACATTTTCTGGAAGGT 
               
               
                   
               
               
                 TTCGATTTTCTGCATTACGACGTTAAAACGGGTGATTTCATCCTGCACTT 
               
               
                   
               
               
                 TAAAATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAA 
               
               
                   
               
               
                 GGCACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATTGAAAATCA 
               
               
                   
               
               
                 TCGTTTCACCGGTCGTTATCGCGATCTGTATCCGGCAAATGAACTGATCG 
               
               
                   
               
               
                 CACTGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCATGGTTGC 
               
               
                   
               
               
                 ACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGCAACCGGTG 
               
               
                   
               
               
                 AAGATTACATTAATAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGAT 
               
               
                   
               
               
                 AGCCGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAA 
               
               
                   
               
               
                 GCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATTGGCTGGCA 
               
               
                   
               
               
                 TATATCCAAGAACTGCGTAAC 
               
            
           
         
       
     
     Additional polynucleotides and polypeptides relevant to this Example include Cas12a variants having single amino acid substitution at M537R and F870L, as shown below. The underlined codons or amino acids correspond to the changes relative to the corresponding WT Cas12a sequences. 
     
       
         
           
               
               
            
               
                   
                   E. coli  optimized DNA M537R 
               
               
                   
                 SEQ ID NO.: 468 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTA 
               
               
                   
               
               
                   
                 GCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAA 
               
               
                   
               
               
                   
                 CCCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGA 
               
               
                   
               
               
                   
                 TAAAGCACGTAACGATCACTACAAAGAACTGAAACCGATT 
               
               
                   
               
               
                   
                 ATCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGC 
               
               
                   
               
               
                   
                 AGCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAAT 
               
               
                   
               
               
                   
                 TGATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAAT 
               
               
                   
               
               
                   
                 GCACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCC 
               
               
                   
               
               
                   
                 ATGATTATTTCATTGGTCGTACCGATAATCTGACCGATGC 
               
               
                   
               
               
                   
                 AATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTT 
               
               
                   
               
               
                   
                 AAAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGG 
               
               
                   
               
               
                   
                 GCACCGTTACCACCACCGAACATGAAAATGCACTGCTGCG 
               
               
                   
               
               
                   
                 TAGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTAT 
               
               
                   
               
               
                   
                 GAGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCA 
               
               
                   
               
               
                   
                 CCGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAA 
               
               
                   
               
               
                   
                 ATTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACC 
               
               
                   
               
               
                   
                 GCAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAA 
               
               
                   
               
               
                   
                 AAGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGT 
               
               
                   
               
               
                   
                 TTTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACC 
               
               
                   
               
               
                   
                 CAGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCC 
               
               
                   
               
               
                   
                 GTGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGT 
               
               
                   
               
               
                   
                 GCTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACAT 
               
               
                   
               
               
                   
                 ATTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCA 
               
               
                   
               
               
                   
                 AACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCT 
               
               
                   
               
               
                   
                 GGAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTT 
               
               
                   
               
               
                   
                 TGCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGG 
               
               
                   
               
               
                   
                 AAACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGA 
               
               
                   
               
               
                   
                 TCTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACC 
               
               
                   
               
               
                   
                 ATTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTA 
               
               
                   
               
               
                   
                 ATGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAA 
               
               
                   
               
               
                   
                 AATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTG 
               
               
                   
               
               
                   
                 AAACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAG 
               
               
                   
               
               
                   
                 CCGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAG 
               
               
                   
               
               
                   
                 CGAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCG 
               
               
                   
               
               
                   
                 CTGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCC 
               
               
                   
               
               
                   
                 TGAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCT 
               
               
                   
               
               
                   
                 GCTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGAT 
               
               
                   
               
               
                   
                 CCGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAA 
               
               
                   
               
               
                   
                 TGGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTA 
               
               
                   
               
               
                   
                 TGCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTG 
               
               
                   
               
               
                   
                 AACTTTCAG CGT CCGACCCTGGCAAGCGGTTGGGATGTTA 
               
               
                   
               
               
                   
                 ATAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAA 
               
               
                   
               
               
                   
                 TGGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGT 
               
               
                   
               
               
                   
                 CGTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCA 
               
               
                   
               
               
                   
                 GTGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGA 
               
               
                   
               
               
                   
                 TGCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAA 
               
               
                   
               
               
                   
                 GCAGTTACCGCACATTTTCAGACCCATACCACCCCGATTC 
               
               
                   
               
               
                   
                 TGCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAA 
               
               
                   
               
               
                   
                 AGAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAA 
               
               
                   
               
               
                   
                 AAATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGA 
               
               
                   
               
               
                   
                 AAGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCAC 
               
               
                   
               
               
                   
                 CCGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATC 
               
               
                   
               
               
                   
                 GATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATC 
               
               
                   
               
               
                   
                 TGGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCA 
               
               
                   
               
               
                   
                 TATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGAC 
               
               
                   
               
               
                   
                 GCAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACA 
               
               
                   
               
               
                   
                 ATAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCT 
               
               
                   
               
               
                   
                 GCATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAAT 
               
               
                   
               
               
                   
                 CTGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAAC 
               
               
                   
               
               
                   
                 TGTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACA 
               
               
                   
               
               
                   
                 TCGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGAC 
               
               
                   
               
               
                   
                 CAGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGT 
               
               
                   
               
               
                   
                 ATGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGA 
               
               
                   
               
               
                   
                 TGAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAA 
               
               
                   
               
               
                   
                 GTTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCG 
               
               
                   
               
               
                   
                 ACAAATTCIIIIIICATGTGCCGATTACCCTGAATTATCA 
               
               
                   
               
               
                   
                 GGCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAAT 
               
               
                   
               
               
                   
                 GCATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTA 
               
               
                   
               
               
                   
                 TTGATCGTGGTGAACGTAACCTGATTTATATCACCGTTAT 
               
               
                   
               
               
                   
                 TGATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAAT 
               
               
                   
               
               
                   
                 ACCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATC 
               
               
                   
               
               
                   
                 GCGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGT 
               
               
                   
               
               
                   
                 TGTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGC 
               
               
                   
               
               
                   
                 CAGGTTATTCATGAAATTGTGGATCTGATGATTCACTATC 
               
               
                   
               
               
                   
                 AGGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAA 
               
               
                   
               
               
                   
                 AAGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAG 
               
               
                   
               
               
                   
                 CAGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGG 
               
               
                   
               
               
                   
                 TGCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCT 
               
               
                   
               
               
                   
                 GAATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCA 
               
               
                   
               
               
                   
                 AAAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGG 
               
               
                   
               
               
                   
                 CACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGT 
               
               
                   
               
               
                   
                 TGATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGC 
               
               
                   
               
               
                   
                 CGCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACG 
               
               
                   
               
               
                   
                 ACGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAA 
               
               
                   
               
               
                   
                 TCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATG 
               
               
                   
               
               
                   
                 CCTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGT 
               
               
                   
               
               
                   
                 TCGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTAT 
               
               
                   
               
               
                   
                 TGTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTAT 
               
               
                   
               
               
                   
                 CGCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGG 
               
               
                   
               
               
                   
                 AAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCT 
               
               
                   
               
               
                   
                 GCCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGAT 
               
               
                   
               
               
                   
                 ACCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTA 
               
               
                   
               
               
                   
                 ATAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCC 
               
               
                   
               
               
                   
                 GGTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTT 
               
               
                   
               
               
                   
                 CAGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTG 
               
               
                   
               
               
                   
                 CATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCA 
               
               
                   
               
               
                   
                 CCTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATT 
               
               
                   
               
               
                   
                 AGCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTA 
               
               
                   
               
               
                   
                 AC 
               
               
                   
               
               
                   
                   E. coli  optimized DNA F870L Cas12a 
               
               
                   
                 SEQ ID NO.: 469 
               
               
                   
                 atgAGGGAGTTTGAAGGTTTGAGGAATGTGTATGAGGTTAGGA 
               
               
                   
               
               
                   
                 AAAGGGTGGGTTTTGAAGTGATTCCGCAGGGTAAAACCCT 
               
               
                   
               
               
                   
                 GAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAA 
               
               
                   
               
               
                   
                 GCACGTAACGATCACTACAAAGAACTGAAACCGATTATCG 
               
               
                   
               
               
                   
                 ACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCT 
               
               
                   
               
               
                   
                 GGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGAT 
               
               
                   
               
               
                   
                 AGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGCAC 
               
               
                   
               
               
                   
                 TGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGA 
               
               
                   
               
               
                   
                 TTATTTCATTGGTCGTACCGATAATCTGACCGATGCAATT 
               
               
                   
               
               
                   
                 AACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAG 
               
               
                   
               
               
                   
                 CCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCAC 
               
               
                   
               
               
                   
                 CGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGC 
               
               
                   
               
               
                   
                 TTTGATAAATTCACCACGTATTTGAGGGGGTTTTATGAGA 
               
               
                   
               
               
                   
                 ATGGGAAAAAGGTGTTTAGGGGAGAAGATATTAGGAGGGG 
               
               
                   
               
               
                   
                 AATTGGGGATGGTATTGTGGAGGATAATTTGGGGAAATTG 
               
               
                   
               
               
                   
                 AAAGAGAAGTGGGAGATTTTTAGGGGTGTGATTAGGGGAG 
               
               
                   
               
               
                   
                 TTGGGAGGGTGGGTGAAGATTTTGAAAAGGTTAAAAAAGG 
               
               
                   
               
               
                   
                 GATGGGGATGTTTGTTAGGAGGAGGATTGAAGAAGTTTTT 
               
               
                   
               
               
                   
                 AGGTTGGGGTTTTAGAATGAGGTGGTGAGGGAGAGGGAGA 
               
               
                   
               
               
                   
                 TTGATGTGTATAAGGAAGTGGTGGGTGGTATTAGCCGTGA 
               
               
                   
               
               
                   
                 AGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTG 
               
               
                   
               
               
                   
                 AATCTGGCCATTCAGAAAAATGATGAAAGGGGAGATATTA 
               
               
                   
               
               
                   
                 TTGGAAGGGTGGGGGATGGTTTTATTGGGGTGTTGAAAGA 
               
               
                   
               
               
                   
                 AATTGTGAGGGATGGTAATAGGGTGAGGTTTATTGTGGAA 
               
               
                   
               
               
                   
                 GAATTGAAATGGGATGAAGAGGTGATTGAGAGGTTTTGGA 
               
               
                   
               
               
                   
                 AATAGAAAAGGCTGCTGCGCAATGAAAATGTTCTGGAAAC 
               
               
                   
               
               
                   
                 TGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTG 
               
               
                   
               
               
                   
                 ACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTT 
               
               
                   
               
               
                   
                 CAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATGC 
               
               
                   
               
               
                   
                 CCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATT 
               
               
                   
               
               
                   
                 ACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAAC 
               
               
                   
               
               
                   
                 ATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGG 
               
               
                   
               
               
                   
                 TAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAA 
               
               
                   
               
               
                   
                 ATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGC 
               
               
                   
               
               
                   
                 CGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAA 
               
               
                   
               
               
                   
                 AAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTG 
               
               
                   
               
               
                   
                 GACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGG 
               
               
                   
               
               
                   
                 AATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGGA 
               
               
                   
               
               
                   
                 AGGGAGGGTGAGGTTTTATAAGAAAGGGGGTAATTATGGG 
               
               
                   
               
               
                   
                 AGGAAAAAAGGGTATAGGGTGGAAAAATTGAAACTGAACT 
               
               
                   
               
               
                   
                 TTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAA 
               
               
                   
               
               
                   
                 AGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGC 
               
               
                   
               
               
                   
                 CTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTT 
               
               
                   
               
               
                   
                 ATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGA 
               
               
                   
               
               
                   
                 AGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCA 
               
               
                   
               
               
                   
                 GCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAG 
               
               
                   
               
               
                   
                 TTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCT 
               
               
                   
               
               
                   
                 GAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAG 
               
               
                   
               
               
                   
                 ATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAAT 
               
               
                   
               
               
                   
                 TCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGG 
               
               
                   
               
               
                   
                 TTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGT 
               
               
                   
               
               
                   
                 GATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATC 
               
               
                   
               
               
                   
                 TGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGG 
               
               
                   
               
               
                   
                 CGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATT 
               
               
                   
               
               
                   
                 AGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAG 
               
               
                   
               
               
                   
                 TTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAA 
               
               
                   
               
               
                   
                 AGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCAT 
               
               
                   
               
               
                   
                 ACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTGG 
               
               
                   
               
               
                   
                 CAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTT 
               
               
                   
               
               
                   
                 TTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCGT 
               
               
                   
               
               
                   
                 CTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGA 
               
               
                   
               
               
                   
                 AAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGA 
               
               
                   
               
               
                   
                 TTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAA 
               
               
                   
               
               
                   
                 GCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTA 
               
               
                   
               
               
                   
                 GCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAA 
               
               
                   
               
               
                   
                 ATTC CTG TTTCATGTGCCGATTACCCTGAATTATCAGGCA 
               
               
                   
               
               
                   
                 GCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCAT 
               
               
                   
               
               
                   
                 ATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGA 
               
               
                   
               
               
                   
                 TCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGAT 
               
               
                   
               
               
                   
                 AGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCA 
               
               
                   
               
               
                   
                 TTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGA 
               
               
                   
               
               
                   
                 GAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTT 
               
               
                   
               
               
                   
                 GGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGG 
               
               
                   
               
               
                   
                 TTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGC 
               
               
                   
               
               
                   
                 CGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGC 
               
               
                   
               
               
                   
                 AAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGT 
               
               
                   
               
               
                   
                 TCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCT 
               
               
                   
               
               
                   
                 GAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                   
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAA 
               
               
                   
               
               
                   
                 TGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCACC 
               
               
                   
               
               
                   
                 GTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGAT 
               
               
                   
               
               
                   
                 CCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCCGCA 
               
               
                   
               
               
                   
                 AACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACGT 
               
               
                   
               
               
                   
                 TAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCGC 
               
               
                   
               
               
                   
                 AATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTACGCCTG 
               
               
                   
               
               
                   
                 CATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCGA 
               
               
                   
               
               
                   
                 TGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGTT 
               
               
                   
               
               
                   
                 CCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGCG 
               
               
                   
               
               
                   
                 ATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAGA 
               
               
                   
               
               
                   
                 GAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCCG 
               
               
                   
               
               
                   
                 AAACTGCTGGAAAATGATGATAGCCATGCAATTGATACCA 
               
               
                   
               
               
                   
                 TGGTTG 
               
               
                   
               
               
                   
                 CACTGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGC 
               
               
                   
               
               
                   
                 AGCAACCGGTGAAGATTACATTAATAGTCCGGTTCGTGAT 
               
               
                   
               
               
                   
                 CTGAATGGTGTTTGTTTTGATAGCCGTTTTCAGAATCCGG 
               
               
                   
               
               
                   
                 AATGGCCGATGGATGCAGATGCAAATGGTGCATATCATAT 
               
               
                   
               
               
                   
                 TGCACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAA 
               
               
                   
               
               
                   
                 AGCAAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGG 
               
               
                   
               
               
                   
                 ATTGGCTGGCATATATCCAAGAACTGCGTAAC 
               
               
                   
               
               
                   
                 Human optimized DNA M537R Cas12a 
               
               
                   
                 SEQ ID NO.: 470 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAG 
               
               
                   
               
               
                   
                 CAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACC 
               
               
                   
               
               
                   
                 CTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATA 
               
               
                   
               
               
                   
                 AAGCACGTAACGATCACTACAAAGAACTGAAACCGATTAT 
               
               
                   
               
               
                   
                 CGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAG 
               
               
                   
               
               
                   
                 CTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTG 
               
               
                   
               
               
                   
                 ATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGC 
               
               
                   
               
               
                   
                 ACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCAT 
               
               
                   
               
               
                   
                 GATTATTTCATTGGTCGTACCGATAATCTGACCGATGCAA 
               
               
                   
               
               
                   
                 TTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAA 
               
               
                   
               
               
                   
                 AGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGC 
               
               
                   
               
               
                   
                 ACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGTA 
               
               
                   
               
               
                   
                 GCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGA 
               
               
                   
               
               
                   
                 GAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACC 
               
               
                   
               
               
                   
                 GCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAAT 
               
               
                   
               
               
                   
                 TCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGC 
               
               
                   
               
               
                   
                 AGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAA 
               
               
                   
               
               
                   
                 GCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTT 
               
               
                   
               
               
                   
                 TTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCA 
               
               
                   
               
               
                   
                 GATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGT 
               
               
                   
               
               
                   
                 GAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGC 
               
               
                   
               
               
                   
                 TGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATAT 
               
               
                   
               
               
                   
                 TATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAA 
               
               
                   
               
               
                   
                 CAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGG 
               
               
                   
               
               
                   
                 AAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTG 
               
               
                   
               
               
                   
                 CAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAA 
               
               
                   
               
               
                   
                 ACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATC 
               
               
                   
               
               
                   
                 TGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCAT 
               
               
                   
               
               
                   
                 TTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAAT 
               
               
                   
               
               
                   
                 GCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAA 
               
               
                   
               
               
                   
                 TTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAA 
               
               
                   
               
               
                   
                 ACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCC 
               
               
                   
               
               
                   
                 GGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCG 
               
               
                   
               
               
                   
                 AAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCT 
               
               
                   
               
               
                   
                 GCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTG 
               
               
                   
               
               
                   
                 AAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGC 
               
               
                   
               
               
                   
                 TGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCC 
               
               
                   
               
               
                   
                 GGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATG 
               
               
                   
               
               
                   
                 GAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATG 
               
               
                   
               
               
                   
                 CCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAA 
               
               
                   
               
               
                   
                 CTTTCAG CGT C 
               
               
                   
               
               
                   
                 CGACCCTGGCAAGCGGTTGGGATGTTAATAAAGAAAAAAA 
               
               
                   
               
               
                   
                 CAACGGTGCCATCCTGTTCGTGAAAAATGGCCTGTATTAT 
               
               
                   
               
               
                   
                 CTGGGTATTATGCCGAAACAGAAAGGTCGTTATAAAGCGC 
               
               
                   
               
               
                   
                 TGAGCTTTGAAGGGAGGGAAAAAAGGAGTGAAGGTTTTGA 
               
               
                   
               
               
                   
                 TAAAATGTAGTAGGAGTATTTTGGGGATGGAGGGAAAATG 
               
               
                   
               
               
                   
                 ATTGGGAAATGTAGGAGGGAGGTGAAAGGAGTTAGGGGAG 
               
               
                   
               
               
                   
                 ATTTTGAGAGGGATAGGAGGGGGATTGTGGTGAGCAATAA 
               
               
                   
               
               
                   
                 CTTTATTGAACCGCTGGAAATCACCAAAGAGATCTACGAT 
               
               
                   
               
               
                   
                 CTGAATAACCCGGAAAAAGAGCCGAAAAAATTCCAGACCG 
               
               
                   
               
               
                   
                 CATATGCAAAAAAAACCGGTGATCAGAAAGGTTATCGTGA 
               
               
                   
               
               
                   
                 AGCGCTGTGTAAATGGATTGATTTGAGGGGTGATTTTCTG 
               
               
                   
               
               
                   
                 AGGAAATAGAGGAAAAGGAGGAGTATGGATGTGAGGAGGG 
               
               
                   
               
               
                   
                 TGGGTGGGAGGAGCCAGTATAAAGATCTGGGCGAATATTA 
               
               
                   
               
               
                   
                 TGCAGAACTGAATCCGCTGCTGTATCATATTAGCTTTCAG 
               
               
                   
               
               
                   
                 CGTATTGCCGAGAAAGAAATCATGGACGCAGTTGAAACCG 
               
               
                   
               
               
                   
                 GTAAACTGTACCTGTTCCAGATCTACAATAAAGATTTTGC 
               
               
                   
               
               
                   
                 CAAAGGCCATCATGGCAAACCGAATCTGCATACCCTGTAT 
               
               
                   
               
               
                   
                 TGGACCGGTCTGTTTAGCCCTGAAAATCTGGGAAAAAGGT 
               
               
                   
               
               
                   
                 GGATTAAAGTGAATGGTGAGGGGGAAGTGTTTTATGGTGG 
               
               
                   
               
               
                   
                 GAAAAGGGGTATGAAAGGTATGGCACATCGTCTGGGTGAA 
               
               
                   
               
               
                   
                 AAAATGCTGAACAAAAAACTGAAAGACCAGAAAACCCCGA 
               
               
                   
               
               
                   
                 TCCCGGATACACTGTATCAAGAACTGTATGATTATGTGAA 
               
               
                   
               
               
                   
                 CCATCGTCTGAGCCATGATCTGAGTGATGAAGCACGTGCC 
               
               
                   
               
               
                   
                 CTGCTGCGGAATGTTATTAGGAAAGAAGTTAGGGAGGAGA 
               
               
                   
               
               
                   
                 TGATTAAAGATGGTGGTTTTAGGAGGGAGAAATTGTTTTT 
               
               
                   
               
               
                   
                 TCATGTGCCGATTACCCTGAATTATCAGGCAGCAAATAGC 
               
               
                   
               
               
                   
                 CCGAGCAAATTTAACCAGCGTGTTAATGCATATCTGAAAG 
               
               
                   
               
               
                   
                 AACATCCAGAAACGCCGATTATTGGTATTGATCGTGGTGA 
               
               
                   
               
               
                   
                 ACGTAACCTGATTTATATCACCGTTATTGATAGCACCGGC 
               
               
                   
               
               
                   
                 AAAATCCTGGAACAGCGTAGCCTGAATACCATTCAGCAGT 
               
               
                   
               
               
                   
                 TTGATTACCAGAAAAAACTGGATAATCGCGAGAAAGAACG 
               
               
                   
               
               
                   
                 TGTTGCAGCACGTCAGGCATGGTCAGTTGTTGGTACAATT 
               
               
                   
               
               
                   
                 AAAGACCTGAAACAGGGTTATCTGAGCCAGGTTATTCATG 
               
               
                   
               
               
                   
                 AAATTGTGGATCTGATGATTCACTATCAGGCCGTTGTTGT 
               
               
                   
               
               
                   
                 GCTGGAAAAGGTGAATTTTGGGTTTAAAAGGAAAGGTAGG 
               
               
                   
               
               
                   
                 GGGATTGGAGAAAAAGGAGTTTATGAGGAGTTGGAGAAAA 
               
               
                   
               
               
                   
                 TGCTGATTGACAAACTGAATTGCCTGGTGCTGAAAGATTA 
               
               
                   
               
               
                   
                 TCCGGCTGAAAAAGTTGGTGGTGTTCTGAATGGGTATGAG 
               
               
                   
               
               
                   
                 GTGAGGGATGAGTTTAGGAGGTTTGGAAAAATGGGGAGGG 
               
               
                   
               
               
                   
                 AGAGGGGATTTGTGTTTTATGTTGGGGGAGGGTATAGGAG 
               
               
                   
               
               
                   
                 GAAAATTGATGGGGTGAGGGGTTTTGTTGATGGGTTTGTT 
               
               
                   
               
               
                   
                 TGGAAAAGGATGAAAAAGGATGAAAGGGGGAAAGATTTTG 
               
               
                   
               
               
                   
                 TGGAAGGTTTGGATTTTGTGGATTAGGAGGTTAAAAGGGG 
               
               
                   
               
               
                   
                 TGATTTGATGGTGGAGTTTAAAATGAATGGGAATGTGAGT 
               
               
                   
               
               
                   
                 TTTGAGGGTGGGGTGGGTGGTTTTATGGGTGGATGGGATA 
               
               
                   
               
               
                   
                 TTGTGTTTGAGAAAAACGAAACACAGTTCGATGCAAAAGG 
               
               
                   
               
               
                   
                 CACCCCGTTTATTGCAGGTAAACGTATTGTTCCGGTGATT 
               
               
                   
               
               
                   
                 GAAAATCATCGTTTCACCGGTCGTTATCGCGATCTGTATC 
               
               
                   
               
               
                   
                 CGGCAAATGAACTGATCGCACTGCTGGAAGAGAAAGGTAT 
               
               
                   
               
               
                   
                 TGTTTTTGGTGATGGGTGAAAGATTGTGGGGAAAGTGGTG 
               
               
                   
               
               
                   
                 GAAAATGATGATAGGGATGGAATTGATACCATGGTTGCAC 
               
               
                   
               
               
                   
                 TGATTCGTAGCGTTCTGCAGATGCGTAATAGCAATGCAGC 
               
               
                   
               
               
                   
                 AACCGGTGAAGATTACATTAATAGTGGGGTTGGTGATGTG 
               
               
                   
               
               
                   
                 AATGGTGTTTGTTTTGATAGGGGTTTTGAGAATGGGGAAT 
               
               
                   
               
               
                   
                 GGGGGATGGATGCAGATGCAAATGGTGCATATCATATTGC 
               
               
                   
               
               
                   
                 ACTGAAAGGACAGCTGCTGCTGAACCACCTGAAAGAAAGC 
               
               
                   
               
               
                   
                 AAAGATCTGAAACTGCAAAACGGCATTAGCAATCAGGATT 
               
               
                   
               
               
                   
                 GGCTGGCATATATCCAAGAACTGCGTAAC 
               
               
                   
               
               
                   
                 Human optimized DNA F870L Cas12a 
               
               
                   
                 SEQ ID NO.: 471 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTAGCA 
               
               
                   
               
               
                   
                 AAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAACCCT 
               
               
                   
               
               
                   
                 GAAACATATTCAAGAACAGGGCTTCATCGAAGAGGATAAA 
               
               
                   
               
               
                   
                 GCACGTAACGATCACTACAAAGAACTGAAACCGATTATCG 
               
               
                   
               
               
                   
                 ACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCAGCT 
               
               
                   
               
               
                   
                 GGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATTGAT 
               
               
                   
               
               
                   
                 AGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATGCAC 
               
               
                   
               
               
                   
                 TGATTGAAGAACAGGCAACCTATCGTAATGCCATCCATGA 
               
               
                   
               
               
                   
                 TTATTTCATTGGTCGTACCGATAATCTGACCGATGCAATT 
               
               
                   
               
               
                   
                 AACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTAAAG 
               
               
                   
               
               
                   
                 CCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGGCAC 
               
               
                   
               
               
                   
                 CGTTACCACCACCGAACATGAAAATGCACTGCTGCGTAGC 
               
               
                   
               
               
                   
                 TTTGATAAATTCACCACCTATTTCAGCGGCTTTTATGAGA 
               
               
                   
               
               
                   
                 ATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCACCGC 
               
               
                   
               
               
                   
                 AATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAATTC 
               
               
                   
               
               
                   
                 AAAGAGAACTGCCACATTTTTACCCGTCTGATTACCGCAG 
               
               
                   
               
               
                   
                 TTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAGC 
               
               
                   
               
               
                   
                 CATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTTTT 
               
               
                   
               
               
                   
                 AGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAGA 
               
               
                   
               
               
                   
                 TTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGTGA 
               
               
                   
               
               
                   
                 AGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCTG 
               
               
                   
               
               
                   
                 AATCTGGCCATTCAGAAAAATGATGAAACCGCACATATTA 
               
               
                   
               
               
                   
                 TTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAACA 
               
               
                   
               
               
                   
                 AATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGAA 
               
               
                   
               
               
                   
                 GAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGCA 
               
               
                   
               
               
                   
                 AATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAAC 
               
               
                   
               
               
                   
                 TGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCTG 
               
               
                   
               
               
                   
                 ACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATTT 
               
               
                   
               
               
                   
                 CAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATGC 
               
               
                   
               
               
                   
                 CCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAATT 
               
               
                   
               
               
                   
                 ACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAAC 
               
               
                   
               
               
                   
                 ATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCGG 
               
               
                   
               
               
                   
                 TAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGAA 
               
               
                   
               
               
                   
                 ATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTGC 
               
               
                   
               
               
                   
                 CGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGAA 
               
               
                   
               
               
                   
                 AAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCTG 
               
               
                   
               
               
                   
                 GACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCGG 
               
               
                   
               
               
                   
                 AATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGGA 
               
               
                   
               
               
                   
                 ACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGCC 
               
               
                   
               
               
                   
                 ACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAACT 
               
               
                   
               
               
                   
                 TTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATAA 
               
               
                   
               
               
                   
                 AGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGGC 
               
               
                   
               
               
                   
                 CTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGTT 
               
               
                   
               
               
                   
                 ATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTGA 
               
               
                   
               
               
                   
                 AGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGCA 
               
               
                   
               
               
                   
                 GCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCAG 
               
               
                   
               
               
                   
                 TTACCGCACATTTTCAGACCCATACCACCCCGATTCTGCT 
               
               
                   
               
               
                   
                 GAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGAG 
               
               
                   
               
               
                   
                 ATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAAT 
               
               
                   
               
               
                   
                 TCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAGG 
               
               
                   
               
               
                   
                 TTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCGT 
               
               
                   
               
               
                   
                 GATTTTCTGAGCAAATACACCAAAACCACCAGTATCGATC 
               
               
                   
               
               
                   
                 TGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGGG 
               
               
                   
               
               
                   
                 CGAATATTATGCAGAACTGAATCCGCTGCTGTATCATATT 
               
               
                   
               
               
                   
                 AGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCAG 
               
               
                   
               
               
                   
                 TTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATAA 
               
               
                   
               
               
                   
                 AGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCAT 
               
               
                   
               
               
                   
                 ACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTGG 
               
               
                   
               
               
                   
                 CAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGTT 
               
               
                   
               
               
                   
                 TTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCGT 
               
               
                   
               
               
                   
                 CTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAGA 
               
               
                   
               
               
                   
                 AAACCCCGATCCCGGATACACTGTATCAAGAACTGTATGA 
               
               
                   
               
               
                   
                 TTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGAA 
               
               
                   
               
               
                   
                 GCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTTA 
               
               
                   
               
               
                   
                 GCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACAA 
               
               
                   
               
               
                   
                 ATTC CTG TTTCATGTGCCGATTACCCTGAATTATCAGGCA 
               
               
                   
               
               
                   
                 GCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCAT 
               
               
                   
               
               
                   
                 ATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTGA 
               
               
                   
               
               
                   
                 TCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGAT 
               
               
                   
               
               
                   
                 AGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACCA 
               
               
                   
               
               
                   
                 TTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCGA 
               
               
                   
               
               
                   
                 GAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGTT 
               
               
                   
               
               
                   
                 GGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAGG 
               
               
                   
               
               
                   
                 TTATTCATGAAATTGTGGATCTGATGATTCACTATCAGGC 
               
               
                   
               
               
                   
                 CGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAGC 
               
               
                   
               
               
                   
                 AAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAGT 
               
               
                   
               
               
                   
                 TCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGCT 
               
               
                   
               
               
                   
                 GAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAAT 
               
               
                   
               
               
                   
                 CCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAAA 
               
               
                   
               
               
                   
                 TGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCAC 
               
               
                   
               
               
                   
                 CGTATACGAGCAAAATTGATCCGCTGACCGG 
               
               
                   
               
               
                   
                 TTTTGTTGATCCGTTTGTTTGGAAAACCATCAAAAACCAT 
               
               
                   
               
               
                   
                 GAAAGCCGCAAACATTTTCTGGAAGGTTTCGATTTTCTGC 
               
               
                   
               
               
                   
                 ATTACGACGTTAAAACGGGTGATTTCATCCTGCACTTTAA 
               
               
                   
               
               
                   
                 AATGAATCGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGT 
               
               
                   
               
               
                   
                 TTTATGCCTGCATGGGATATTGTGTTTGAGAAAAACGAAA 
               
               
                   
               
               
                   
                 CACAGTTCGATGCAAAAGGCACCCCGTTTATTGCAGGTAA 
               
               
                   
               
               
                   
                 ACGTATTGTTCCGGTGATTGAAAATCATCGTTTCACCGGT 
               
               
                   
               
               
                   
                 CGTTATCGCGATCTGTATCCGGCAAATGAACTGATCGCAC 
               
               
                   
               
               
                   
                 TGCTGGAAGAGAAAGGTATTGTTTTTCGTGATGGCTCAAA 
               
               
                   
               
               
                   
                 CATTCTGCCGAAACTGCTGGAAAATGATGATAGCCATGCA 
               
               
                   
               
               
                   
                 ATTGATACCATGGTTGCACTGATTCGTAGCGTTCTGCAGA 
               
               
                   
               
               
                   
                 TGCGTAATAGCAATGCAGCAACCGGTGAAGATTACATTAA 
               
               
                   
               
               
                   
                 TAGTCCGGTTCGTGATCTGAATGGTGTTTGTTTTGATAGC 
               
               
                   
               
               
                   
                 CGTTTTCAGAATCCGGAATGGCCGATGGATGCAGATGCAA 
               
               
                   
               
               
                   
                 ATGGTGCATATCATATTGCACTGAAAGGACAGCTGCTGCT 
               
               
                   
               
               
                   
                 GAACCACCTGAAAGAAAGCAAAGATCTGAAACTGCAAAAC 
               
               
                   
               
               
                   
                 GGCATTAGCAATCAGGATTGGCTGGCATATATCCAAGAAC 
               
               
                   
               
               
                   
                 TGCGTAAC 
               
               
                   
               
               
                   
                 M537R Cas12a AA 
               
               
                   
                 SEQ ID NO : 472 
               
               
                   
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEED 
               
               
                   
               
               
                   
                 KARNDHYKELKPIIDRIYKTYADQCL 
               
               
                   
               
               
                   
                 QLVQLDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAI 
               
               
                   
               
               
                   
                 HDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQL 
               
               
                   
               
               
                   
                 GTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDIS 
               
               
                   
               
               
                   
                 TAIPHRIVQDNFPKFKENCHIFTRLITAVPSLREHFENVK 
               
               
                   
               
               
                   
                 KAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGGIS 
               
               
                   
               
               
                   
                 REAGTEKIKGLNEVLNLAIQKNDETAHIIASLPHRFIPLF 
               
               
                   
               
               
                   
                 KQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVL 
               
               
                   
               
               
                   
                 ETAEALFNELNSIDLTHIFISHKKLETISSALCDHWDTLR 
               
               
                   
               
               
                   
                 NALYERRISELTGKITKSAKEKVQRSLKHEDINLQEIISA 
               
               
                   
               
               
                   
                 AGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEI 
               
               
                   
               
               
                   
                 LKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARLTGIKLE 
               
               
                   
               
               
                   
                 MEPSLSFYNKARNYATKKPYSVEKFKLNFQ R PTLASGWDV 
               
               
                   
               
               
                   
                 NKEKNNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKT 
               
               
                   
               
               
                   
                 SEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPI 
               
               
                   
               
               
                   
                 LLSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQ 
               
               
                   
               
               
                   
                 KGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKD 
               
               
                   
               
               
                   
                 LGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIY 
               
               
                   
               
               
                   
                 NKDFAKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAE 
               
               
                   
               
               
                   
                 LFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPDTLYQEL 
               
               
                   
               
               
                   
                 YDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTS 
               
               
                   
               
               
                   
                 DKFFFHVPITLNYQAANSPSKFNQRVNAYLKEHPETPIIGI 
               
               
                   
               
               
                   
                 DRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDNR 
               
               
                   
               
               
                   
                 EKERVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHYQ 
               
               
                   
               
               
                   
                 AVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLIDKLNCLV 
               
               
                   
               
               
                   
                 LKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVPA 
               
               
                   
               
               
                   
                 PYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHYD 
               
               
                   
               
               
                   
                 VKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQF 
               
               
                   
               
               
                   
                 DAKGTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALLE 
               
               
                   
               
               
                   
                 EKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSVLQMRN 
               
               
                   
               
               
                   
                 SNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANGA 
               
               
                   
               
               
                   
                 YHIALKGQLLLNHLKESKDLKLQNGISNQDWLAYIQELRN 
               
               
                   
               
               
                   
                 F870L Cas12a AA 
               
               
                   
                 SEQ ID NO.: 473 
               
               
                   
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQGFIEED 
               
               
                   
               
               
                   
                 KARNDHYKELKPIIDRIYKTYADQCL 
               
               
                   
               
               
                   
                 QLVQLDWENLSAAIDSYRKEKTEETRNALIEEQATYRNAI 
               
               
                   
               
               
                   
                 HDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNGKVLKQL 
               
               
                   
               
               
                   
                 GTVTTTEHENALLRSFDKFTTYFSGFYENRKNVFSAEDIS 
               
               
                   
               
               
                   
                 TAIPHRIVQDNFPKFKENCHIFTRLITAVPSLREHFENVK 
               
               
                   
               
               
                   
                 KAIGIFVSTSIEEVFSFPFYNQLLTQTQIDLYNQLLGGIS 
               
               
                   
               
               
                   
                 REAGTEKIKGLNEVLNLAIQKNDETAHIIASLPHRFIPLF 
               
               
                   
               
               
                   
                 KQILSDRNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVL 
               
               
                   
               
               
                   
                 ETAEALFNELNSIDLTHIFISHKKLETISSALCDHWDTLR 
               
               
                   
               
               
                   
                 NALYERRISELTGKITKSAKEKVQRSLKHEDINLQEIISA 
               
               
                   
               
               
                   
                 AGKELSEAFKQKTSEILSHAHAALDQPLPTTLKKQEEKEI 
               
               
                   
               
               
                   
                 LKSQLDSLLGLYHLLDWFAVDESNEVDPEFSARLTGIKLE 
               
               
                   
               
               
                   
                 MEPSLSFYNKARNYATKKPYSVEKFKLNFQMPTLASGWDV 
               
               
                   
               
               
                   
                 NKEKNNGAILFVKNGLYYLGIMPKQKGRYKALSFEPTEKT 
               
               
                   
               
               
                   
                 SEGFDKMYYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPI 
               
               
                   
               
               
                   
                 LLSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGDQ 
               
               
                   
               
               
                   
                 KGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRPSSQYKD 
               
               
                   
               
               
                   
                 LGEYYAELNPLLYHISFQRIAEKEIMDAVETGKLYLFQIY 
               
               
                   
               
               
                   
                 NKDFAKGHHGKPNLHTLYWTGLFSPENLAKTSIKLNGQAE 
               
               
                   
               
               
                   
                 LFYRPKSRMKRMAHRLGEKMLNKKLKDQKTPIPDTLYQEL 
               
               
                   
               
               
                   
                 YDYVNHRLSHDLSDEARALLPNVITKEVSHEIIKDRRFTS 
               
               
                   
               
               
                   
                 DKF L FHVPITLNYQAANSPSKFNQRVNAYLKEHPETPIIG 
               
               
                   
               
               
                   
                 IDRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLDN 
               
               
                   
               
               
                   
                 REKERVAARQAWSVVGTIKDLKQGYLSQVIHEIVDLMIHY 
               
               
                   
               
               
                   
                 OAVVVLENLNFGFKSKRTGIAEKAVYQQFEKMLIDKLNCL 
               
               
                   
               
               
                   
                 VLKDYPAEKVGGVLNPYQLTDQFTSFAKMGTQSGFLFYVP 
               
               
                   
               
               
                   
                 APYTSKIDPLTGFVDPFVWKTIKNHESRKHFLEGFDFLHY 
               
               
                   
               
               
                   
                 DVKTGDFILHFKMNRNLSFQRGLPGFMPAWDIVFEKNETQ 
               
               
                   
               
               
                   
                 FDAKGTPFIAGKRIVPVIENHRFTGRYRDLYPANELIALL 
               
               
                   
               
               
                   
                 EEKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSVLQMR 
               
               
                   
               
               
                   
                 NSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPMDADANG 
               
               
                   
               
               
                   
                 AYHIALKGQLLLNHLKESKDLKLQNGISNQDWLAYIQELR 
               
               
                   
               
               
                   
                 N 
               
            
           
         
       
     
     Example 6. Rational Design of Fusion Cas12a Polypeptides 
     Fusion Cas12/a polypeptides having additional motifs enabling nuclear localization into eukaryotic cells (collectively, “NLS” or “NLS sequences”), and/or purification and label detection motifs (collectively, “affinity tags”) fall within the scope of the present invention. Exemplary nuclear localization signals (“NLS” or “NLS sequences”) are well known in the art and include those listed identified by polynucleotide and amino acid sequences depicted in Table 6. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Exemplary NLS sequences 
               
            
           
           
               
               
               
               
            
               
                   
                 SEQ ID 
                 NLS 
                   
               
               
                   
                 NO.: 
                 Name 
                 Sequence (5′→3′ or N→C) 
               
               
                   
               
               
                   
                 474 
                 SV40 
                 CCGAAAAAAAAACGTAAAGTTGG 
               
               
                   
               
               
                   
                 475 
                 SV40 
                 PKKKRKV 
               
               
                   
               
               
                   
                 476 
                 OpT 
                 AGCAGTGATGATGAAGCAACCG 
               
               
                   
                   
                   
                 CAGATAGCCAGCATGCAGCACC 
               
               
                   
                   
                   
                 GCCTAAAAAGAAACGTAAAGTT 
               
               
                   
               
               
                   
                 477 
                 OpT 
                 SSDDEATADSQHAAPPKKKRKV 
               
               
                   
               
               
                   
                 478 
                 aNLS 
                 CCGCCTCCGAAACGTCCGCGTC 
               
               
                   
                   
                   
                 TGGAT 
               
               
                   
               
               
                   
                 479 
                 aNLS 
                 PPPKRPRLD 
               
               
                   
               
               
                   
                 480 
                 BIP1 
                 AAACGTCCGGCAGCAACCAAAA 
               
               
                   
                   
                   
                 AAGCAGGTCAGGCAAAAAAGAA 
               
               
                   
                   
                   
                 AAAA 
               
               
                   
               
               
                   
                 481 
                 BIP1 
                 KRPAATKKAGQAKKKK 
               
               
                   
               
               
                   
                 482 
                 BIP2 
                 AAACGTACCGCAGATGGTAGCG 
               
               
                   
                   
                   
                 AATTTGAAAGCCCGAAAAAAAA 
               
               
                   
                   
                   
                 GCGTAAGGTGGAA 
               
               
                   
               
               
                   
                 483 
                 BIP2 
                 KRTADGSEEESPKKKRKVE 
               
               
                   
               
            
           
         
       
     
     Exemplary purification and/or label detection motifs include affinity tags that are also well known in the art. Often, additional amino acid linkers inserted before or after the additional motifs can provide improvements in expression and/or stability of the expressed fusion Cas12/a polypeptide. Two examples of affinity tags are defined by polynucleotide and amino acid sequences depicted below in Table 7. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Exemplary affinity tags 
               
            
           
           
               
               
               
               
            
               
                   
                 SEQ 
                 Affinity 
                   
               
               
                   
                 ID 
                 Tag 
                 Sequence 
               
               
                   
                 NO.: 
                 Name 
                 (5′→3′ or N→C) 
               
               
                   
               
               
                   
                 484 
                 V5 
                 GGTAAACCGATTCCGAATCCGC 
               
               
                   
                   
                   
                 TGCTGGGTCTGGATAGCACC 
               
               
                   
               
               
                   
                 485 
                 V5 
                 GKPIPNPLLGLDST 
               
               
                   
               
               
                   
                 486 
                 HIS 
                 CACCACCACCACCACCAC 
               
               
                   
               
               
                   
                 487 
                 HIS 
                 HHHHHH 
               
               
                   
               
            
           
         
       
     
     Fusion Cas12a polypeptides that include a nuclear localization signal, linker amino acids and/or affinity tags can be readily constructed using chemical polypeptide methods or expressed from engineered polynucleotides encoding in-frame polypeptides created with recombinant DNA technology. Such technologies are well known and within the purview of one skilled in the art. Working examples of such polynucleotides and polypeptides are illustrated by SEQ ID NOs.: 5-30. Fusion Cas12a polypeptide variants that encode the open reading frames of SEQ ID NOs.: 59-245 having nuclear localization sequences and/or affinity tags and optionally amino acid linkers as needed fall within the scope of this disclosure. Exemplary Cas12a variants having nuclear localization signals are presented below. 
     Briefly, the method of site directed mutagenesis (SDM) was employed to create the expression constructs having As Cas12a coding sequences with different nuclear localization signals (NLS&#39;s). Site directed mutagenesis was performed by designing complimentary primers that encompass the desired nucleotide base change(s), along with flanking plasmid vector sequence, wherein each flanking region has a melting temperature (T m ) of at least 60° C. A polymerase chain reaction (PCR) run was then performed using standard cycling conditions for a total of 16 cycles. The restriction enzyme, DPN I, was added to digest away the starting plasmid vector material so only the new product containing the base changes remain. After DPN I treatment, a small amount of the PCR product was transformed into competent  E. coli  cells, recovered in SOC media and plated onto kanamycin resistance Luria Broth (LB) agar plates. Colonies were screened using the Sanger sequencing method to verify correct base changes in selected clones. 
     
       
         
           
               
            
               
                   E. coli  optimized DNA WT Cas12a with NLS linkers 
               
               
                 SEQ ID NO.: 488 
               
               
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTA 
               
               
                   
               
               
                 GCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAAC 
               
               
                   
               
               
                 CCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGAT 
               
               
                   
               
               
                 AAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTA 
               
               
                   
               
               
                 TCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATT 
               
               
                   
               
               
                 GATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATG 
               
               
                   
               
               
                 CACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCA 
               
               
                   
               
               
                 TGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCA 
               
               
                   
               
               
                 ATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGG 
               
               
                   
               
               
                 CACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGT 
               
               
                   
               
               
                 AGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATG 
               
               
                   
               
               
                 AGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCAC 
               
               
                   
               
               
                 CGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCG 
               
               
                   
               
               
                 CAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAA 
               
               
                   
               
               
                 AGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTT 
               
               
                   
               
               
                 TTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCC 
               
               
                   
               
               
                 AGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTG 
               
               
                   
               
               
                 CTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATA 
               
               
                   
               
               
                 TTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAA 
               
               
                   
               
               
                 ACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTG 
               
               
                   
               
               
                 GAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGA 
               
               
                   
               
               
                 AACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGAT 
               
               
                   
               
               
                 CTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCA 
               
               
                   
               
               
                 TTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAA 
               
               
                   
               
               
                 TGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGA 
               
               
                   
               
               
                 AACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGC 
               
               
                   
               
               
                 CGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGC 
               
               
                   
               
               
                 GAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGC 
               
               
                   
               
               
                 TGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTG 
               
               
                   
               
               
                 CTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATC 
               
               
                   
               
               
                 CGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTAT 
               
               
                   
               
               
                 GCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                 ACTTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAA 
               
               
                   
               
               
                 TAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAAT 
               
               
                   
               
               
                 GGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTC 
               
               
                   
               
               
                 GTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAG 
               
               
                   
               
               
                 TGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAG 
               
               
                   
               
               
                 CAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCT 
               
               
                   
               
               
                 GCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAA 
               
               
                   
               
               
                 GAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAA 
               
               
                   
               
               
                 AATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACC 
               
               
                   
               
               
                 CGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCG 
               
               
                   
               
               
                 ATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCT 
               
               
                   
               
               
                 GGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCAT 
               
               
                   
               
               
                 ATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAA 
               
               
                   
               
               
                 TAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTG 
               
               
                   
               
               
                 CATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATC 
               
               
                   
               
               
                 TGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACT 
               
               
                   
               
               
                 GTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACC 
               
               
                   
               
               
                 AGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTA 
               
               
                   
               
               
                 TGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGAT 
               
               
                   
               
               
                 GAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAG 
               
               
                   
               
               
                 TTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                 CAAATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAG 
               
               
                   
               
               
                 GCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATG 
               
               
                   
               
               
                 CATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTAT 
               
               
                   
               
               
                 TGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCG 
               
               
                   
               
               
                 CGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTT 
               
               
                   
               
               
                 GTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCC 
               
               
                   
               
               
                 AGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCA 
               
               
                   
               
               
                 GGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGC 
               
               
                   
               
               
                 AGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGT 
               
               
                   
               
               
                 GCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTG 
               
               
                   
               
               
                 AATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAA 
               
               
                   
               
               
                 AAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTT 
               
               
                   
               
               
                 GATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCC 
               
               
                   
               
               
                 GCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGA 
               
               
                   
               
               
                 CGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAAT 
               
               
                   
               
               
                 CGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTT 
               
               
                   
               
               
                 CGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATT 
               
               
                   
               
               
                 GTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATC 
               
               
                   
               
               
                 GCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGA 
               
               
                   
               
               
                 AGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATA 
               
               
                   
               
               
                 CCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAA 
               
               
                   
               
               
                 TAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCG 
               
               
                   
               
               
                 GTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTC 
               
               
                   
               
               
                 AGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCAC 
               
               
                   
               
               
                 CTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTA 
               
               
                   
               
               
                 GCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTA 
               
               
                   
               
               
                 AC GGTCGT   AGCAGTGATGATGAAGCAACCGCAGATAGCCA   
               
               
                   
               
               
                 
                   GCATGCAGCACCGCCTAAAAAGAAACGTAAAGTT 
                   GGTGGT 
                 
               
               
                   
               
               
                 
                   AGCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAG 
                 
               
               
                   
               
               
                 
                   GGGGTTCTGGTGGCTCTGGTGGTAGCctcgag 
                   caccacca 
                 
               
               
                   
               
               
                 
                   ccaccaccac 
                 
               
            
           
         
       
     
     The underlined sequences refer to nucleotides encoding amino acid linker sequences. The double-underlined sequences refer to nucleotides encoding nuclear localization sequences (NLS linker). The italicized sequences refer to nucleotides encoding amino acid affinity tag sequences ((HIS) 6 ). 
     
       
         
           
               
               
            
               
                   
                   E. coli  optimized DNA M537R F870L 
               
               
                   
                 Cas12a with NLS linkers 
               
               
                   
                 SEQ ID NO. 489 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTA 
               
               
                   
               
               
                   
                 GCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAAC 
               
               
                   
               
               
                   
                 CCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGAT 
               
               
                   
               
               
                   
                 AAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTA 
               
               
                   
               
               
                   
                 TCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                   
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATT 
               
               
                   
               
               
                   
                 GATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATG 
               
               
                   
               
               
                   
                 CACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCA 
               
               
                   
               
               
                   
                 TGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCA 
               
               
                   
               
               
                   
                 ATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                   
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGG 
               
               
                   
               
               
                   
                 CACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGT 
               
               
                   
               
               
                   
                 AGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATG 
               
               
                   
               
               
                   
                 AGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCAC 
               
               
                   
               
               
                   
                 CGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                   
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCG 
               
               
                   
               
               
                   
                 CAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAA 
               
               
                   
               
               
                   
                 AGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTT 
               
               
                   
               
               
                   
                 TTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCC 
               
               
                   
               
               
                   
                 AGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                   
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTG 
               
               
                   
               
               
                   
                 CTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATA 
               
               
                   
               
               
                   
                 TTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAA 
               
               
                   
               
               
                   
                 ACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTG 
               
               
                   
               
               
                   
                 GAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                   
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGA 
               
               
                   
               
               
                   
                 AACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGAT 
               
               
                   
               
               
                   
                 CTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCA 
               
               
                   
               
               
                   
                 TTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAA 
               
               
                   
               
               
                   
                 TGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                   
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGA 
               
               
                   
               
               
                   
                 AACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGC 
               
               
                   
               
               
                   
                 CGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGC 
               
               
                   
               
               
                   
                 GAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGC 
               
               
                   
               
               
                   
                 TGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                   
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTG 
               
               
                   
               
               
                   
                 CTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATC 
               
               
                   
               
               
                   
                 CGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                   
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTAT 
               
               
                   
               
               
                   
                 GCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                   
                 ACTTTCAG  CCGACCCTGGCAAGCGGTTGGGATGTTAA 
               
               
                   
               
               
                   
                 TAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAAT 
               
               
                   
               
               
                   
                 GGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTC 
               
               
                   
               
               
                   
                 GTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAG 
               
               
                   
               
               
                   
                 TGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                   
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAG 
               
               
                   
               
               
                   
                 CAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCT 
               
               
                   
               
               
                   
                 GCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAA 
               
               
                   
               
               
                   
                 GAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAA 
               
               
                   
               
               
                   
                 AATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                   
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACC 
               
               
                   
               
               
                   
                 CGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCG 
               
               
                   
               
               
                   
                 ATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCT 
               
               
                   
               
               
                   
                 GGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCAT 
               
               
                   
               
               
                   
                 ATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                   
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAA 
               
               
                   
               
               
                   
                 TAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTG 
               
               
                   
               
               
                   
                 CATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATC 
               
               
                   
               
               
                   
                 TGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACT 
               
               
                   
               
               
                   
                 GTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                   
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACC 
               
               
                   
               
               
                   
                 AGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTA 
               
               
                   
               
               
                   
                 TGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGAT 
               
               
                   
               
               
                   
                 GAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAG 
               
               
                   
               
               
                   
                 TTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                   
                 CAAATTCCTGTTTCATGTGCCGATTACCCTGAATTATCAG 
               
               
                   
               
               
                   
                 GCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATG 
               
               
                   
               
               
                   
                 CATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTAT 
               
               
                   
               
               
                   
                 TGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                   
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                   
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCG 
               
               
                   
               
               
                   
                 CGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTT 
               
               
                   
               
               
                   
                 GTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCC 
               
               
                   
               
               
                   
                 AGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCA 
               
               
                   
               
               
                   
                 GGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                   
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGC 
               
               
                   
               
               
                   
                 AGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGT 
               
               
                   
               
               
                   
                 GCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTG 
               
               
                   
               
               
                   
                 AATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAA 
               
               
                   
               
               
                   
                 AAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                   
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTT 
               
               
                   
               
               
                   
                 GATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCC 
               
               
                   
               
               
                   
                 GCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGA 
               
               
                   
               
               
                   
                 CGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAAT 
               
               
                   
               
               
                   
                 CGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                   
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTT 
               
               
                   
               
               
                   
                 CGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATT 
               
               
                   
               
               
                   
                 GTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATC 
               
               
                   
               
               
                   
                 GCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGA 
               
               
                   
               
               
                   
                 AGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                   
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATA 
               
               
                   
               
               
                   
                 CCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAA 
               
               
                   
               
               
                   
                 TAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCG 
               
               
                   
               
               
                   
                 GTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTC 
               
               
                   
               
               
                   
                 AGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                   
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCAC 
               
               
                   
               
               
                   
                 CTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTA 
               
               
                   
               
               
                   
                 GCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAA 
               
               
                   
               
               
                   
                 C GGTCGT   AGCAGTGATGATGAAGCAACCGCAGATAGCCAG   
               
               
                   
               
               
                   
                 
                   CATGCAGCACCGCCTAAAAAGAAACGTAAAGTT 
                   GGTGGTA 
                 
               
               
                   
               
               
                   
                 
                   GCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGG 
                 
               
               
                   
               
               
                   
                 
                   GGGTTCTGGTGGCTCTGGTGGTAGCctcgag 
                   caccaccac 
                 
               
               
                   
               
               
                   
                 
                   caccaccac 
                 
               
            
           
         
       
     
     The bolded and underlined sequences refer to mutant codons introduced into the Cas12a open reading frame. The underlined sequences refer to nucleotides encoding amino acid linker sequences. The double-underlined sequences refer to nucleotides encoding nuclear localization sequences (NLS linker). The italicized sequences refer to nucleotides encoding amino acid affinity tag sequences ((HIS) 6 ). 
     
       
         
           
               
               
            
               
                   
                 Human optimized DNA WT Casl2a with NLS linkers 
               
               
                   
                 SEQ ID NO: 490 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTA 
               
               
                   
               
               
                   
                 GCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAAC 
               
               
                   
               
               
                   
                 CCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGAT 
               
               
                   
               
               
                   
                 AAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTA 
               
               
                   
               
               
                   
                 TCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                   
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATT 
               
               
                   
               
               
                   
                 GATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATG 
               
               
                   
               
               
                   
                 CACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCA 
               
               
                   
               
               
                   
                 TGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCA 
               
               
                   
               
               
                   
                 ATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                   
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGG 
               
               
                   
               
               
                   
                 CACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGT 
               
               
                   
               
               
                   
                 AGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATG 
               
               
                   
               
               
                   
                 AGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCAC 
               
               
                   
               
               
                   
                 CGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                   
                 TTCAAAGAGAACTGCCACATmTACCCGTCTGATTACCGCA 
               
               
                   
               
               
                   
                 GTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAAAG 
               
               
                   
               
               
                   
                 CCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTTTT 
               
               
                   
               
               
                   
                 TAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCCAG 
               
               
                   
               
               
                   
                 ATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCGTG 
               
               
                   
               
               
                   
                 AAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTGCT 
               
               
                   
               
               
                   
                 GAATCTGGCCATTCAGAAAAATGATGAAACCGCACATATT 
               
               
                   
               
               
                   
                 ATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAAAC 
               
               
                   
               
               
                   
                 AAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTGGA 
               
               
                   
               
               
                   
                 AGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTTGC 
               
               
                   
               
               
                   
                 AAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGAAA 
               
               
                   
               
               
                   
                 CTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGATCT 
               
               
                   
               
               
                   
                 GACCCACATCTTTATCAGCCACAAAAAACTGGAAACCATT 
               
               
                   
               
               
                   
                 TCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAATG 
               
               
                   
               
               
                   
                 CCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAAAT 
               
               
                   
               
               
                   
                 TACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGAAA 
               
               
                   
               
               
                   
                 CATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGCCG 
               
               
                   
               
               
                   
                 GTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGCGA 
               
               
                   
               
               
                   
                 AATTCTGTCACATGCACATGCAGCACTGGATCAGCCGCTG 
               
               
                   
               
               
                   
                 CCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCTGA 
               
               
                   
               
               
                   
                 AAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTGCT 
               
               
                   
               
               
                   
                 GGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATCCG 
               
               
                   
               
               
                   
                 GAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAATGG 
               
               
                   
               
               
                   
                 AACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTATGC 
               
               
                   
               
               
                   
                 CACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGAAC 
               
               
                   
               
               
                   
                 TTTCAGATGCCGACCCTGGCAAGCGGTTGGGATGTTAATA 
               
               
                   
               
               
                   
                 AAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAATGG 
               
               
                   
               
               
                   
                 CCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTCGT 
               
               
                   
               
               
                   
                 TATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAGTG 
               
               
                   
               
               
                   
                 AAGGTTTTGATAAAATGTACTACGACTATTTTCCGGATGC 
               
               
                   
               
               
                   
                 AGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAGCA 
               
               
                   
               
               
                   
                 GTTACCGCACATTTTCAGACCCATACCACCCCGATTCTGC 
               
               
                   
               
               
                   
                 TGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAAGA 
               
               
                   
               
               
                   
                 GATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAAAA 
               
               
                   
               
               
                   
                 TTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAAAG 
               
               
                   
               
               
                   
                 GTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACCCG 
               
               
                   
               
               
                   
                 TGATTTTCTGAGCAAATACACCAAAACCACCAGTATCGAT 
               
               
                   
               
               
                   
                 CTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCTGG 
               
               
                   
               
               
                   
                 GCGAATATTATGCAGAACTGAATCCGCTGCTGTATCATAT 
               
               
                   
               
               
                   
                 TAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACGCA 
               
               
                   
               
               
                   
                 GTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAATA 
               
               
                   
               
               
                   
                 AAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTGCA 
               
               
                   
               
               
                   
                 TACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATCTG 
               
               
                   
               
               
                   
                 GCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACTGT 
               
               
                   
               
               
                   
                 TTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACATCG 
               
               
                   
               
               
                   
                 TCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACCAG 
               
               
                   
               
               
                   
                 AAAACCCCGATCCCGGATACACTGTATCAAGAACTGTATG 
               
               
                   
               
               
                   
                 ATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGATGA 
               
               
                   
               
               
                   
                 AGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAGTT 
               
               
                   
               
               
                   
                 AGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGACA 
               
               
                   
               
               
                   
                 AATTCTTTTTTCATGTGCCGATTACCCTGAATTATCAGGC 
               
               
                   
               
               
                   
                 AGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATGCA 
               
               
                   
               
               
                   
                 TATCTGAAAGAACATCCAGAAACGCCGATTATTGGTATTG 
               
               
                   
               
               
                   
                 ATCGTGGTGAACGTAACCTGATTTATATCACCGTTATTGA 
               
               
                   
               
               
                   
                 TAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATACC 
               
               
                   
               
               
                   
                 ATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCGCG 
               
               
                   
               
               
                   
                 AGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTTGT 
               
               
                   
               
               
                   
                 TGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCCAG 
               
               
                   
               
               
                   
                 GTTATTCATGAAATTGTGGATCTGATGATTCACTATCAGG 
               
               
                   
               
               
                   
                 CCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAAAG 
               
               
                   
               
               
                   
                 CAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGCAG 
               
               
                   
               
               
                   
                 TTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGTGC 
               
               
                   
               
               
                   
                 TGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTGAA 
               
               
                   
               
               
                   
                 TCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAAAA 
               
               
                   
               
               
                   
                 ATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGCAC 
               
               
                   
               
               
                   
                 CGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTTGA 
               
               
                   
               
               
                   
                 TCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCCGC 
               
               
                   
               
               
                   
                 AAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGACG 
               
               
                   
               
               
                   
                 TTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAATCG 
               
               
                   
               
               
                   
                 CAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGCCT 
               
               
                   
               
               
                   
                 GCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTTCG 
               
               
                   
               
               
                   
                 ATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATTGT 
               
               
                   
               
               
                   
                 TCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATCGC 
               
               
                   
               
               
                   
                 GATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGAAG 
               
               
                   
               
               
                   
                 AGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTGCC 
               
               
                   
               
               
                   
                 GAAACTGCTGGAAAATGATGATAGCCATGCAATTGATACC 
               
               
                   
               
               
                   
                 ATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAATA 
               
               
                   
               
               
                   
                 GCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCGGT 
               
               
                   
               
               
                   
                 TCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTCAG 
               
               
                   
               
               
                   
                 AATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGCAT 
               
               
                   
               
               
                   
                 ATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCACCT 
               
               
                   
               
               
                   
                 GAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTAGC 
               
               
                   
               
               
                   
                 AATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAAC G   
               
               
                   
               
               
                   
                 
                   GTCGT 
                   AGCAGTGATGATGAAGCAACCGCAGATAGCCAGCA 
                 
               
               
                   
               
               
                   
                 
                   TGCAGCACCGCCTAAAAAGAAACGTAAAGTT 
                   GGTGGTAGC 
                 
               
               
                   
               
               
                   
                 
                   GGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGGGG 
                 
               
               
                   
               
               
                   
                 
                   GTTCTGGTGGCTCTGGTGGTAGCctcgag 
                   caccaccacca 
                 
               
               
                   
               
               
                   
                 
                   ccaccac 
                 
               
            
           
         
       
     
     The underlined sequences refer to nucleotides encoding amino acid linker sequences. The double-underlined sequences refer to nucleotides encoding nuclear localization sequences (NLS linker). The italicized sequences refer to nucleotides encoding amino acid affinity tag sequences ((HIS) 6 ). 
     
       
         
           
               
               
            
               
                   
                 Human optimized DNA M537R F870L 
               
               
                   
                 Cas12a with NLS linkers 
               
               
                   
                 SEQ ID NO : 491 
               
               
                   
                 atgACCCAGTTTGAAGGTTTCACCAATCTGTATCAGGTTA 
               
               
                   
               
               
                   
                 GCAAAACCCTGCGTTTTGAACTGATTCCGCAGGGTAAAAC 
               
               
                   
               
               
                   
                 CCTGAAACATATTCAAGAACAGGGCTTCATCGAAGAGGAT 
               
               
                   
               
               
                   
                 AAAGCACGTAACGATCACTACAAAGAACTGAAACCGATTA 
               
               
                   
               
               
                   
                 TCGACCGCATCTATAAAACCTATGCAGATCAGTGTCTGCA 
               
               
                   
               
               
                   
                 GCTGGTTCAGCTGGATTGGGAAAATCTGAGCGCAGCAATT 
               
               
                   
               
               
                   
                 GATAGTTATCGCAAAGAAAAAACCGAAGAAACCCGTAATG 
               
               
                   
               
               
                   
                 CACTGATTGAAGAACAGGCAACCTATCGTAATGCCATCCA 
               
               
                   
               
               
                   
                 TGATTATTTCATTGGTCGTACCGATAATCTGACCGATGCA 
               
               
                   
               
               
                   
                 ATTAACAAACGTCACGCCGAAATCTATAAAGGCCTGTTTA 
               
               
                   
               
               
                   
                 AAGCCGAACTGTTTAATGGCAAAGTTCTGAAACAGCTGGG 
               
               
                   
               
               
                   
                 CACCGTTACCACCACCGAACATGAAAATGCACTGCTGCGT 
               
               
                   
               
               
                   
                 AGCTTTGATAAATTCACCACCTATTTCAGCGGCTTTTATG 
               
               
                   
               
               
                   
                 AGAATCGCAAAAACGTGTTTAGCGCAGAAGATATTAGCAC 
               
               
                   
               
               
                   
                 CGCAATTCCGCATCGTATTGTGCAGGATAATTTCCCGAAA 
               
               
                   
               
               
                   
                 TTCAAAGAGAACTGCCACATTTTTACCCGTCTGATTACCG 
               
               
                   
               
               
                   
                 CAGTTCCGAGCCTGCGTGAACATTTTGAAAACGTTAAAAA 
               
               
                   
               
               
                   
                 AGCCATCGGCATCTTTGTTAGCACCAGCATTGAAGAAGTT 
               
               
                   
               
               
                   
                 TTTAGCTTCCCGTTTTACAATCAGCTGCTGACCCAGACCC 
               
               
                   
               
               
                   
                 AGATTGATCTGTATAACCAACTGCTGGGTGGTATTAGCCG 
               
               
                   
               
               
                   
                 TGAAGCAGGCACCGAAAAAATCAAAGGTCTGAATGAAGTG 
               
               
                   
               
               
                   
                 CTGAATCTGGCCATTCAGAAAAATGATGAAACCGCACATA 
               
               
                   
               
               
                   
                 TTATTGCAAGCCTGCCGCATCGTTTTATTCCGCTGTTCAA 
               
               
                   
               
               
                   
                 ACAAATTCTGAGCGATCGTAATACCCTGAGCTTTATTCTG 
               
               
                   
               
               
                   
                 GAAGAATTCAAATCCGATGAAGAGGTGATTCAGAGCTTTT 
               
               
                   
               
               
                   
                 GCAAATACAAAACGCTGCTGCGCAATGAAAATGTTCTGGA 
               
               
                   
               
               
                   
                 AACTGCCGAAGCACTGTTTAACGAACTGAATAGCATTGAT 
               
               
                   
               
               
                   
                 CTGACCCACATCTTTATCAGCCACAAAAAACTGGAAACCA 
               
               
                   
               
               
                   
                 TTTCAAGCGCACTGTGTGATCATTGGGATACCCTGCGTAA 
               
               
                   
               
               
                   
                 TGCCCTGTATGAACGTCGTATTAGCGAACTGACCGGTAAA 
               
               
                   
               
               
                   
                 ATTACCAAAAGCGCGAAAGAAAAAGTTCAGCGCAGTCTGA 
               
               
                   
               
               
                   
                 AACATGAGGATATTAATCTGCAAGAGATTATTAGCGCAGC 
               
               
                   
               
               
                   
                 CGGTAAAGAACTGTCAGAAGCATTTAAACAGAAAACCAGC 
               
               
                   
               
               
                   
                 GAAATTCTGTCACATGCACATGCAGCACTGGATCAGCCGC 
               
               
                   
               
               
                   
                 TGCCGACCACCCTGAAAAAACAAGAAGAAAAAGAAATCCT 
               
               
                   
               
               
                   
                 GAAAAGCCAGCTGGATAGCCTGCTGGGTCTGTATCATCTG 
               
               
                   
               
               
                   
                 CTGGACTGGTTTGCAGTTGATGAAAGCAATGAAGTTGATC 
               
               
                   
               
               
                   
                 CGGAATTTAGCGCACGTCTGACCGGCATTAAACTGGAAAT 
               
               
                   
               
               
                   
                 GGAACCGAGCCTGAGCTTTTATAACAAAGCCCGTAATTAT 
               
               
                   
               
               
                   
                 GCCACCAAAAAACCGTATAGCGTCGAAAAATTCAAACTGA 
               
               
                   
               
               
                   
                 ACTTTCAG CGT CCGACCCTGGCAAGCGGTTGGGATGTTAA 
               
               
                   
               
               
                   
                 TAAAGAAAAAAACAACGGTGCCATCCTGTTCGTGAAAAAT 
               
               
                   
               
               
                   
                 GGCCTGTATTATCTGGGTATTATGCCGAAACAGAAAGGTC 
               
               
                   
               
               
                   
                 GTTATAAAGCGCTGAGCTTTGAACCGACGGAAAAAACCAG 
               
               
                   
               
               
                   
                 TGAAGGTTTTGATAAAATGTACTACGACTATTTTCCGGAT 
               
               
                   
               
               
                   
                 GCAGCCAAAATGATTCCGAAATGTAGCACCCAGCTGAAAG 
               
               
                   
               
               
                   
                 CAGTTACCGCACATTTTCAGACCCATACCACCCCGATTCT 
               
               
                   
               
               
                   
                 GCTGAGCAATAACTTTATTGAACCGCTGGAAATCACCAAA 
               
               
                   
               
               
                   
                 GAGATCTACGATCTGAATAACCCGGAAAAAGAGCCGAAAA 
               
               
                   
               
               
                   
                 AATTCCAGACCGCATATGCAAAAAAAACCGGTGATCAGAA 
               
               
                   
               
               
                   
                 AGGTTATCGTGAAGCGCTGTGTAAATGGATTGATTTCACC 
               
               
                   
               
               
                   
                 CGTGATTTTCTGAGCAAATACACCAAAACCACCAGTATCG 
               
               
                   
               
               
                   
                 ATCTGAGCAGCCTGCGTCCGAGCAGCCAGTATAAAGATCT 
               
               
                   
               
               
                   
                 GGGCGAATATTATGCAGAACTGAATCCGCTGCTGTATCAT 
               
               
                   
               
               
                   
                 ATTAGCTTTCAGCGTATTGCCGAGAAAGAAATCATGGACG 
               
               
                   
               
               
                   
                 CAGTTGAAACCGGTAAACTGTACCTGTTCCAGATCTACAA 
               
               
                   
               
               
                   
                 TAAAGATTTTGCCAAAGGCCATCATGGCAAACCGAATCTG 
               
               
                   
               
               
                   
                 CATACCCTGTATTGGACCGGTCTGTTTAGCCCTGAAAATC 
               
               
                   
               
               
                   
                 TGGCAAAAACCTCGATTAAACTGAATGGTCAGGCGGAACT 
               
               
                   
               
               
                   
                 GTTTTATCGTCCGAAAAGCCGTATGAAACGTATGGCACAT 
               
               
                   
               
               
                   
                 CGTCTGGGTGAAAAAATGCTGAACAAAAAACTGAAAGACC 
               
               
                   
               
               
                   
                 AGAAAACCCCGATCCCGGATACACTGTATCAAGAACTGTA 
               
               
                   
               
               
                   
                 TGATTATGTGAACCATCGTCTGAGCCATGATCTGAGTGAT 
               
               
                   
               
               
                   
                 GAAGCACGTGCCCTGCTGCCGAATGTTATTACCAAAGAAG 
               
               
                   
               
               
                   
                 TTAGCCACGAGATCATTAAAGATCGTCGTTTTACCAGCGA 
               
               
                   
               
               
                   
                 CAAATTC CTG TTTCATGTGCCGATTACCCTGAATTATCAG 
               
               
                   
               
               
                   
                 GCAGCAAATAGCCCGAGCAAATTTAACCAGCGTGTTAATG 
               
               
                   
               
               
                   
                 CATATCTGAAAGAACATCCAGAAACGCCGATTATTGGTAT 
               
               
                   
               
               
                   
                 TGATCGTGGTGAACGTAACCTGATTTATATCACCGTTATT 
               
               
                   
               
               
                   
                 GATAGCACCGGCAAAATCCTGGAACAGCGTAGCCTGAATA 
               
               
                   
               
               
                   
                 CCATTCAGCAGTTTGATTACCAGAAAAAACTGGATAATCG 
               
               
                   
               
               
                   
                 CGAGAAAGAACGTGTTGCAGCACGTCAGGCATGGTCAGTT 
               
               
                   
               
               
                   
                 GTTGGTACAATTAAAGACCTGAAACAGGGTTATCTGAGCC 
               
               
                   
               
               
                   
                 AGGTTATTCATGAAATTGTGGATCTGATGATTCACTATCA 
               
               
                   
               
               
                   
                 GGCCGTTGTTGTGCTGGAAAACCTGAATTTTGGCTTTAAA 
               
               
                   
               
               
                   
                 AGCAAACGTACCGGCATTGCAGAAAAAGCAGTTTATCAGC 
               
               
                   
               
               
                   
                 AGTTCGAGAAAATGCTGATTGACAAACTGAATTGCCTGGT 
               
               
                   
               
               
                   
                 GCTGAAAGATTATCCGGCTGAAAAAGTTGGTGGTGTTCTG 
               
               
                   
               
               
                   
                 AATCCGTATCAGCTGACCGATCAGTTTACCAGCTTTGCAA 
               
               
                   
               
               
                   
                 AAATGGGCACCCAGAGCGGATTTCTGTTTTATGTTCCGGC 
               
               
                   
               
               
                   
                 ACCGTATACGAGCAAAATTGATCCGCTGACCGGTTTTGTT 
               
               
                   
               
               
                   
                 GATCCGTTTGTTTGGAAAACCATCAAAAACCATGAAAGCC 
               
               
                   
               
               
                   
                 GCAAACATTTTCTGGAAGGTTTCGATTTTCTGCATTACGA 
               
               
                   
               
               
                   
                 CGTTAAAACGGGTGATTTCATCCTGCACTTTAAAATGAAT 
               
               
                   
               
               
                   
                 CGCAATCTGAGTTTTCAGCGTGGCCTGCCTGGTTTTATGC 
               
               
                   
               
               
                   
                 CTGCATGGGATATTGTGTTTGAGAAAAACGAAACACAGTT 
               
               
                   
               
               
                   
                 CGATGCAAAAGGCACCCCGTTTATTGCAGGTAAACGTATT 
               
               
                   
               
               
                   
                 GTTCCGGTGATTGAAAATCATCGTTTCACCGGTCGTTATC 
               
               
                   
               
               
                   
                 GCGATCTGTATCCGGCAAATGAACTGATCGCACTGCTGGA 
               
               
                   
               
               
                   
                 AGAGAAAGGTATTGTTTTTCGTGATGGCTCAAACATTCTG 
               
               
                   
               
               
                   
                 CCGAAACTGCTGGAAAATGATGATAGCCATGCAATTGATA 
               
               
                   
               
               
                   
                 CCATGGTTGCACTGATTCGTAGCGTTCTGCAGATGCGTAA 
               
               
                   
               
               
                   
                 TAGCAATGCAGCAACCGGTGAAGATTACATTAATAGTCCG 
               
               
                   
               
               
                   
                 GTTCGTGATCTGAATGGTGTTTGTTTTGATAGCCGTTTTC 
               
               
                   
               
               
                   
                 AGAATCCGGAATGGCCGATGGATGCAGATGCAAATGGTGC 
               
               
                   
               
               
                   
                 ATATCATATTGCACTGAAAGGACAGCTGCTGCTGAACCAC 
               
               
                   
               
               
                   
                 CTGAAAGAAAGCAAAGATCTGAAACTGCAAAACGGCATTA 
               
               
                   
               
               
                   
                 GCAATCAGGATTGGCTGGCATATATCCAAGAACTGCGTAA 
               
               
                   
               
               
                   
                 C GGTCGT   AGCAGTGATGATGAAGCAACCGCAGATAGCCAG   
               
               
                   
               
               
                   
                 
                   CATGCAGCACCGCCTAAAAAGAAACGTAAAGTTG 
                   GTGGTA 
                 
               
               
                   
               
               
                   
                 
                   GCGGTGGTTCAGGTGGTAGTGGCGGTAGTGGTGGCTCAGG 
                 
               
               
                   
               
               
                   
                 
                   GGGTTCTGGTGGCTCTGGTGGTAGCctcgag 
                   caccaccac 
                 
               
               
                   
               
               
                   
                 
                   caccaccac 
                 
               
            
           
         
       
     
     The bolded and underlined sequences refer to mutant codons introduced into the Cas12a open reading frame. The underlined sequences refer to nucleotides encoding amino acid linker sequences. The double-underlined sequences refer to nucleotides encoding nuclear localization sequences (NLS linker). The italicized sequences refer to nucleotides encoding amino acid affinity tag sequences ((HIS) 6 ). 
     
       
         
           
               
               
            
               
                   
                 WT Cas12a AA with NLS linkers 
               
               
                   
                 SEQ ID NO.: 492 
               
               
                   
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQG 
               
               
                   
               
               
                   
                 FIEEDKARNDHYKELKPilDRIYKTYADQCLQL 
               
               
                   
               
               
                   
                 VQLDWENLSAAIDSYRKEKTEETRNALIEEQATY 
               
               
                   
               
               
                   
                 RNAIHDYFIGRTDNLTDAINKRHAEIYKGLFKAEL 
               
               
                   
               
               
                   
                 FNGKVLKQLGTVTTTEHENALLRSFDKFTTYFSGF 
               
               
                   
               
               
                   
                 YENRKNVFSAEDISTAIPHRIVQDNFPKFKENCHI 
               
               
                   
               
               
                   
                 FTRLITAVPSLREHFENVKKAIGIFVSTSIEEVFS 
               
               
                   
               
               
                   
                 FPFYNQLLTQTQIDLYNQLLGGISREAGTEKIKGL 
               
               
                   
               
               
                   
                 NEVLNLAIQKNDETAHIIASLPHRFIPLFKQILSD 
               
               
                   
               
               
                   
                 RNTLSFILEEFKSDEEVIQSFCKYKTLLRNENVLE 
               
               
                   
               
               
                   
                 TAEALFNELNSIDLTHIFISHKKLETISSALCDHW 
               
               
                   
               
               
                   
                 DTLRNALYERRISELTGKITKSAKEKVQRSLKHED 
               
               
                   
               
               
                   
                 INLQEIISAAGKELSEAFKQKTSEILSHAHAALDQ 
               
               
                   
               
               
                   
                 PLPTTLKKQEEKEILKSQLDSLLGLYHLLDWFAVD 
               
               
                   
               
               
                   
                 ESNEVDPEFSARLTGIKLEMEPSLSFYNKARNYAT 
               
               
                   
               
               
                   
                 KKPYSVEKFKLNFQMPTLASGWDVNKEKNNGAILF 
               
               
                   
               
               
                   
                 VKNGLYYLGIMPKQKGRYKALSFEPTEKTSEGFDK 
               
               
                   
               
               
                   
                 MYYDYFPDAAKMIPKCSTQLKAVTAHFQTHTTPIL 
               
               
                   
               
               
                   
                 LSNNFIEPLEITKEIYDLNNPEKEPKKFQTAYAKK 
               
               
                   
               
               
                   
                 TGDQKGYREALCKWIDFTRDFLSKYTKTTSIDLSS 
               
               
                   
               
               
                   
                 LRPSSQYKDLGEYYAELNPLLYHISFQRIAEKEIM 
               
               
                   
               
               
                   
                 DAVETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTG 
               
               
                   
               
               
                   
                 LFSPENLAKTSIKLNGQAELFYRPKSRMKRMAHRL 
               
               
                   
               
               
                   
                 GEKMLNKKLKDQKTPIPDTLYQELYDYVNHRLSHD 
               
               
                   
               
               
                   
                 LSDEARALLPNVITKEVSHEIIKDRRFTSDKFFFH 
               
               
                   
               
               
                   
                 VPITLNYQAANSPSKFNQRVNAYLKEHPETPIIGI 
               
               
                   
               
               
                   
                 DRGERNLIYITVIDSTGKILEQRSLNTIQQFDYQK 
               
               
                   
               
               
                   
                 KLDNREKERVAARQAWSVVGTIKDLKQGYLSQVIH 
               
               
                   
               
               
                   
                 EIVDLMIHYQAVVVLENLNFGFKSKRTGIAEKAVY 
               
               
                   
               
               
                   
                 QQFEKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTD 
               
               
                   
               
               
                   
                 QFTSFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDP 
               
               
                   
               
               
                   
                 FVWKTIKNHESRKHFLEGFDFLHYDVKTGDFILHF 
               
               
                   
               
               
                   
                 KMNRNLSFQRGLPGFMPAWDIVFEKNETQFDAKGT 
               
               
                   
               
               
                   
                 PFIAGKRIVPVIENHRFTGRYRDLYPANELIALLE 
               
               
                   
               
               
                   
                 EKGIVFRDGSNILPKLLENDDSHAIDTMVALIRSV 
               
               
                   
               
               
                   
                 LQMRNSNAATGEDYINSPVRDLNGVCFDSRFQNPE 
               
               
                   
               
               
                   
                 WPMDADANGAYHIALKGQLLLNHLKESKDLKLQNG 
               
               
                   
               
               
                   
                 ISNQDWLAYIQELRN GR   
               
               
                   
               
               
                   
                 
                   SSDDEATADSQHAAPPKKKRKV 
                   GGSGGSGGSGG 
                 
               
               
                   
               
               
                   
                 
                   SGGSGGSGGSGGSLE 
                   HHHHHH 
                 
               
            
           
         
       
     
     The underlined sequences refer to amino acid sequences encoding amino acid linker sequences. The double-underlined sequences refer to amino acid sequences encoding nuclear localization sequences (NLS linker). The italicized sequences refer to amino acid sequences encoding amino acid affinity tag sequences ((HIS) 6 ). 
     
       
         
           
               
               
            
               
                   
                 M537R F870L Cas12a AA with NLS linkers 
               
               
                   
                 SEQ ID NO.: 493 
               
               
                   
                 MTQFEGFTNLYQVSKTLRFELIPQGKTLKHIQEQG 
               
               
                   
               
               
                   
                 FIEEDKARNDHYKELKPIIDRIYKTYADQCLQLVQ 
               
               
                   
               
               
                   
                 LDWENLSAAIDSYRKEKTEETRNALIEEQATYRNA 
               
               
                   
               
               
                   
                 IHDYFIGRTDNLTDAINKRHAEIYKGLFKAELFNG 
               
               
                   
               
               
                   
                 KVLKQLGTVTTTEHENALLRSFDKFTTYFSGFYEN 
               
               
                   
               
               
                   
                 RKNVFSAEDISTAIPHRIVQDNFPKFKENCHIFTR 
               
               
                   
               
               
                   
                 LITAVPSLREHFENVKKAIGIFVSTSIEEVFSFPF 
               
               
                   
               
               
                   
                 YNQLLTQTQIDLYNQLLGGISREAGTEKIKGLNEV 
               
               
                   
               
               
                   
                 LNLAIQKNDETAHIIASLPHRFIPLFKQILSDRNT 
               
               
                   
               
               
                   
                 LSFILEEFKSDEEVIQSFCKYKTLLRNENVLETAE 
               
               
                   
               
               
                   
                 ALFNELNSIDLTHIFISHKKLETISSALCDHWDTL 
               
               
                   
               
               
                   
                 RNALYERRISELTGKITKSAKEKVQRSLKHEDINL 
               
               
                   
               
               
                   
                 QEIISAAGKELSEAFKQKTSEILSHAHAALDQPLP 
               
               
                   
               
               
                   
                 TTLKKQEEKEILKSQLDSLLGLYHLLDWFAVDESN 
               
               
                   
               
               
                   
                 EVDPEFSARLTGIKLEMEPSLSFYNKARNYATKKP 
               
               
                   
               
               
                   
                 YSVEKFKLNFQ   R   PTLASGWDVNKEKNNGAILFVKN 
               
               
                   
               
               
                   
                 GLYYLGIMPKQKGRYKALSFEPTEKTSEGFDKMYY 
               
               
                   
               
               
                   
                 DYFPDAAKMIPKCSTQLKAVTAHFQTHTTPILLSN 
               
               
                   
               
               
                   
                 NFIEPLEITKEIYDLNNPEKEPKKFQTAYAKKTGD 
               
               
                   
               
               
                   
                 QKGYREALCKWIDFTRDFLSKYTKTTSIDLSSLRP 
               
               
                   
               
               
                   
                 SSQYKDLGEYYAELNPLLYHISFQRIAEKEIMDAV 
               
               
                   
               
               
                   
                 ETGKLYLFQIYNKDFAKGHHGKPNLHTLYWTGLFS 
               
               
                   
               
               
                   
                 PENLAKTSIKLNGQAELFYRPKSRMKRMAHRLGEK 
               
               
                   
               
               
                   
                 MLNKKLKDQKTPIPDTLYQELYDYVNHRLSHDLSD 
               
               
                   
               
               
                   
                 EARALLPNVITKEVSHEIIKDRRFTSDKF   L   FHVPI 
               
               
                   
               
               
                   
                 TLNYQAANSPSKFNQRVNAYLKEHPETPIIGIDRG 
               
               
                   
               
               
                   
                 ERNLIYITVIDSTGKILEQRSLNTIQQFDYQKKLD 
               
               
                   
               
               
                   
                 NREKERVAARQAWSVVGTIKDLKQGYLSQVIHEIV 
               
               
                   
               
               
                   
                 DLMIHYQAVVVLENLNFGFKSKRTGIAEKAVYQQF 
               
               
                   
               
               
                   
                 EKMLIDKLNCLVLKDYPAEKVGGVLNPYQLTDQFT 
               
               
                   
               
               
                   
                 SFAKMGTQSGFLFYVPAPYTSKIDPLTGFVDPFVW 
               
               
                   
               
               
                   
                 KTIKNHESRKHFLEGFDFLHYDVKTGDFILHFKMN 
               
               
                   
               
               
                   
                 RNLSFQRGLPGFMPAWDIVFEKNETQFDAKGTPFI 
               
               
                   
               
               
                   
                 AGKRIVPVIENHRFTGRYRDLYPANELIALLEEKG 
               
               
                   
               
               
                   
                 IVFRDGSNILPKLLENDDSHAIDTMVALIRSVLQM 
               
               
                   
               
               
                   
                 RNSNAATGEDYINSPVRDLNGVCFDSRFQNPEWPM 
               
               
                   
               
               
                   
                 DADANGAYHIALKGQLLLNHLKESKDLKLQNGISN 
               
               
                   
               
               
                   
                 QDWLAYIQELRN GRS   SDDEATADSQHAAPPKKKRK   
               
               
                   
               
               
                   
                 
                   V 
                   GGSGGSGGSGGSGGSGGSGGSGGSLE 
                   HHHHHH 
                 
               
            
           
         
       
     
     The bolded and underlined sequences refer to mutant amino acids introduced into the Cas12a polypeptide variant. The underlined sequences refer to amino acid sequences encoding amino acid linker sequences. The double-underlined sequences refer to amino acid sequences encoding nuclear localization sequences (NLS linker). The italicized sequences refer to amino acid sequences encoding amino acid affinity tag sequences ((HIS) 6 ). 
     REFERENCES 
     
         
         Chen, J. S., et al.,  Enhanced proofreading governs CRISPR - Cas 9  targeting accuracy . Nature, 2017. 550(7676): p. 407-410. 
         Gao, L., et al.,  Engineered Cpf 1  variants with altered PAM specificities increase genome targeting range . Nat Biotechnol. 2017; 35(8): 789-792. 
         Jinek M, et al.  A programmable dual - RNA—guided DNA endonuclease in adaptive bacterial immunity . Science. 2012; 337:816-821. doi: 10.1126/science.1225829. 
         Kleinstiver, B. P., et al.,  High - fidelity CRISPR - Cas 9  nucleases with no detectable genome - wide off - target effects . Nature, 2016. 529(7587): p. 490-5. 
         Slaymaker, I. M., et al.,  Rationally engineered Cas 9  nucleases with improved specificity . Science, 2016. 351(6268): p. 84-8. 
         Sun, Y., et al.,  Factors influencing the nuclear targeting ability of nuclear localization signals . J Drug Target, 2016. 24(10): p. 927-933. 
         Wrenbeck E E, Klesmith J R, Stapleton J A, Adeniran A, Tyo K E, Whitehead TA. Plasmid-based one-pot saturation mutagenesis.  Nat Methods.  2016; 13(11):928-930. doi:10.1038/nmeth.4029 
         Zetsche, B., et al., Cpf1  Is a Single RNA - Guided Endonuclease of a Class  2  CRISPR - Cas System . Cell. 2015; 163:759-771. doi: 10.1016/j.ce11.2015.09.038. 
       
    
     INCORPORATION BY REFERENCE 
     All of the patents, patent applications, patent application publications, and other publications cited herein are hereby incorporated by reference as if set forth in their entirety. 
     Preferred Embodiments 
     The present invention has been described in connection with what are presently considered to be the most practical and preferred embodiments. However, the invention has been presented by way of illustration and is not intended to be limited to the disclosed embodiments. Accordingly, one of skill in the art will realize that the invention is intended to encompass all modifications and alternative arrangements within the spirit and scope of the invention as set forth in the appended claims.