Genomic Sequencing to Aid Diagnosis in Pediatric and Prenatal Practice: Examining Clinical Utility, Ethical Implications, Payer Coverage, and Data Integration in a Diverse Population.
Phase: NA
Conditions: Encephalopathy, Birth Defect, Intellectual Disability, Multiple Congenital Anomaly, Metabolic Disease, Epilepsy, Neuro-Degenerative Disease, Cerebral Palsy, Developmental Delay, Developmental Defect
Sponsor: University of California, San Francisco

Clinical Utility of Pediatric Whole Exome Sequencing 
NCT03525431 
Document Date: 02/09/2022 

Study Application (Version 1.34)
1.0
General Information
*Enter the full title of your study:
Program in Prenatal and Pediatric Genome Sequencing (P3EGS)
 
 
*Enter the study alias:
P3EGS
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this 
study.
 
 
2.0
Add departments
2.1 and Specify Research Location:
Is 
Primary? Department Name
UCSF - 
 - CHO - Peds Neurology
707812
UCSF - 
 - M_PEDS-MEDICAL GENETICS
136225
UCSF - 
 - SOM NEUROLOGY PEDIATRIC
707440
 
3.0
List the key study personnel: (Note: external and affiliated collaborators who 
are not in the UCSF directory can be identified later in the Qualifications of 
Key Study Personnel section at the end of the form)
3.1 *Please add a Principal Investigator for the study:
 
Norton, Mary MD, MD
Select if applicable
Department Chair
Resident
Fellow
If the Principal Investigator is a Fellow, the name of the Faculty Advisor must be supplied below.
 
3.2 If applicable, please select the Research Staff personnel
 
A) Additional Investigators
Curry, Cynthia 
 Study Clinician
Gallagher, Renata MD, PhD , MD, PhD 
 Study Clinician
Gangaram, Balram 
 Study Clinician
Gardner, Marisa A 
N

 Study Clinician
Klein, Ophir MD 
 Study Clinician
Koenig, Barbara, PhD 
 Other Investigator
Sherr, Elliott MD, PhD 
 Study Clinician
Shieh, Joseph, MD, PhD 
 Study Clinician
Strober, Jonathan 
 Study Clinician
Tam, Allison C 
 Study Clinician
Tenney, Jessica L 
 Study Clinician
Weiss, William MD, PhD 
 Study Clinician
B) Research Support Staff
Ackerman, Sara, PhD, MPH 
 Clinical Research Associate
Anguiano, Beatriz 
 Study Coordinator
Chang, Jiyoo 
 Research Assistant
Chen, Flavia H 
 Data Manager
Chin, Garrett 
 Data Manager
Fairley, Cecilia F 
 Clinical Research Associate
Faubel, Amanda J 
 Research Assistant
Hoban, Hannah G 
 Study Coordinator
Lianoglou, Billie R 
 Study Recruiter
Outram, Simon M 
 Clinical Research Associate
Patel, Sachi 
 Study Coordinator
Prasad, Hannah L 
 Study Coordinator
Rego, Shannon M 
 Study Recruiter
Sahin Hodoglugil, Nuriye N 
 Study Coordinator
Yip, Tiffany A 
 Study Recruiter
3.3 *Please add a Study Contact
 
Koenig, Barbara, PhD 

Norton, Mary MD, MD 
Rego, Shannon M 
Sahin Hodoglugil, Nuriye N 
Slavotinek, Anne PhD, PhD 
Yip, Tiffany A 
The Study Contact(s) will receive all important system notifications along with the Principal 
Investigator. (e.g. The project contact(s) are typically either the Study Coordinator or the Principal 
Investigator themselves).
3.4 If applicable, please add a Faculty Advisor/Mentor:
 
3.5 If applicable, please select the Designated Department Approval(s)
 
Add the name of the individual authorized to approve and sign off on this protocol from your 
Department (e.g. the Department Chair or Dean).
4.0
 
Initial Screening Questions 
Updated April 2020 - Revised Common Rule (January 2018) Compliant / COVID-19 - 
v94
4.1  * 
:
PROJECT SUMMARY  (REQUIRED) Give a brief overview of this project (250 words or less). Tell us 
what this study is about, who is being studied, and what it aims to achieve. If you have an NIH 
Abstract, paste it here (Click on the orange question mark to the right for more detailed instructions):
Exome sequencing, which allows physicians to look at many genes concurrently, has been rapidly 
integrated into the clinical setting but its usefulness remains uncertain. The UCSF Program in 
Prenatal and Pediatric Genome Sequencing (P3EGS) will study the effectiveness of sequencing as 
a tool for 1) diagnosing infants and children with serious suspected genetic conditions, including 
developmental disorders. We will also address ethical, social and economic issues in the delivery 
of genomic sequencing results to diverse populations, such as under represented minorities and 
the medically underserved.
4.2  
 
* 
:
HUD DEVICE (REQUIRED) 
 
Does this application involve a Humanitarian Use Device (HUD):
No 
Yes, and it includes a research component 
Yes, and it involves clinical care ONLY 
4.3  * 
: 
TYPE OF RESEARCH (REQUIRED) 
(
Select the option that best fits your project Click the orange 
question mark to the right for definitions and guidance):
Biomedical research (including medical records review, biospecimen collection and/or use, 
other healthcare or health outcomes related activities, research database, biospecimen bank, 
or recruitment registry) 
Social, behavioral, educational, and/or public policy research 
Hybrid - includes aspects of BOTH types of research (check this option if your research is 
mainly social/behavioral but also involves specimen collection or blood draws to look at 
biological measures) 
4.4  * 
 
SUBJECT CONTACT: (REQUIRED) Does this study involve 
 contact or interactions with 
ANY
participants:

Yes (including phone, email or web contact) 
No (limited to medical records review, biological specimen analysis, and/or data analysis) 
4.5  
 
* RISK LEVEL: (REQUIRED) What is your estimation of the risk level, including all screening 
:
procedures and study activities
Minimal risk 
Greater than minimal risk 
4.6  * REVIEW LEVEL: (REQUIRED) Requested review level (Click on the orange question mark to the 
right for definitions and guidance):
Full Committee 
Expedited 
Exempt 
4.7  
 
* EXPEDITED REVIEW CATEGORIES: (REQUIRED) If you think this study qualifies for expedited 
 
 
review, select the regulatory categories that the research falls under: (check all that apply)
Category 1: Research using approved drugs or devices being used for their approved 
indications
Category 2: Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture 
in certain populations and within certain amounts
Category 3: Prospective collection of biological specimens for research purposes by 
noninvasive means (e.g. buccal swabs, urine, hair and nail clippings, etc.)
Category 4: Collection of data through noninvasive, routine clinical procedures (e.g. physical 
sensors such as pulse oximeters, MRI, EKG, EEG, ultrasound, moderate exercise testing, etc. 
- no sedation, general anesthesia, x-rays or microwaves)
Category 5: Research involving materials (data, documents, records, or specimens) that have 
been or will be collected solely for nonresearch purposes
Category 6: Collection of data from voice, video, digital, or image recordings made for 
research purposes
Category 7: Research on individual or group characteristics or behavior or research employing 
survey, interview, oral history, focus group, program evaluation, human factorsevaluation, or 
quality assurance methodologies
* Does the collection of blood samples meet requirements outlined by HHS 
Office for Human Research Protections for Expedited Review Research 
: 
Category 2
(REQUIRED)
For healthy, nonpregnant adults who weigh at least 110 pounds the 
amounts drawn may not exceed 550 ml in an 8 week period and 
collection may not occur more frequently than 2 times per week;
From other adults and children, considering the age, weight, and 
health of the subjects, the collection procedure, the amount of blood 
to be collected, and the frequency with which it will be collected, the 
amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in 
an 8 week period and collection may not occur more frequently than 2 
times per week
 Yes  
 No
4.9  
 
* DATA/SPECIMEN ANALYSIS ONLY: (REQUIRED) Does this study 
 involve records review and
ONLY
/or biospecimen analysis (do not check 'Yes' if this is a registry, research or recruitment database, or 
biospecimen repository):

  Yes  
  No
4.10  
 
* CLINICAL TRIAL: (REQUIRED)
Is this a clinical trial:
According to The World Health Organization (WHO) and the 
International Committee of Medical Journal Editors (ICMJE) a 
clinical trial is:
Any research study that prospectively assigns human participants or 
groups of humans to one or more health-related interventions to 
evaluate the effects on health outcomes.
ICMJE requires 
 of a clinical trial in a public database (such as 
registration
ClinicalTrials.gov) prior to enrollment, for eventual publication of results in 
member biomedical journals.
Public Law 110-85 requires that all investigators who perform 
Guidance: 
an 
 must ensure that the trial is registered on a 
applicable clinical trial
 
.
government web site called ClinicalTrials.gov
 
The FDA requires registration for 'applicable clinical trials,' defined 
as follows:
For any trials of drugs and biologics: controlled clinical investigations, 
other than Phase 1 investigations, of a product subject to FDA 
regulation.
For trials of biomedical devices: controlled trials with health outcomes 
of devices subject to FDA regulation, other than small feasibility 
studies, and pediatric post-market surveillance.
 
 
For additional information on the ClinicalTrials.gov registration process at 
UCSF and the definition of a clinical trial for purposes of registration, visit 
 
the ClinicalTrials.gov section of the UCSF Clinical Research Resource 
HUB.
 
 
 Yes  
 No
 - 'NCT' number for this trial:
Clinical Trial Registration
NCT03525431
4.11  * 
: 
CLINICAL TRIAL PHASE (REQUIRED) Check the applicable phase(s):
Phase 0
Phase 1
Phase 1/2
Phase 2
Phase 2/3
Phase 3
Phase 4
Not Applicable

4.12  
: 
* INVESTIGATOR-INITIATED (REQUIRED) Is this an investigator-initiated study:
 Yes  
 No
 of the 
 to 
The UCSF IRB recommends use
Virtual Regulatory Binder
manage your study.
4.13  * 
 
CORONAVIRUS RESEARCH: (REQUIRED) Does this study involve research on coronaviruses (COVID-
19, SARS, MERS or other):
  Yes  
  No
4.15  
 
*
 
CANCER: (REQUIRED) Does this study involve cancer (e.g., the study involves patients with cancer 
or at risk for cancer, including behavioral research, epidemiological research, public policy research, 
specimen analysis, and chart reviews):
  Yes  
  No
4.16  * 
 
RADIATION EXPOSURE: (REQUIRED) Does your protocol involve any radiation exposure to patients
/subjects 
 from 
 
for 
 purposes (e.g., x-rays, CT-scans, DEXA, CT-
EITHER
standard care OR 
research
guided biopsy, radiation therapy, or nuclear medicine including PET, MUGA or bone scans):
  Yes  
  No
4.17  SCIENTIFIC REVIEW: If this study has undergone scientific or scholarly review, please indicate 
which entity performed the review (check all that apply):
Cancer Center Protocol Review Committee (PRC) (Full approval is required prior to final IRB 
approval for cancer-related protocols.)
CTSI Clinical Research Services (CRS) Advisory Committee
CTSI Consultation Services
Departmental scientific review
Other:
 
* Specify Other: (REQUIRED)
NHGRI, NIH
4.18  
 
* STEM CELLS: (REQUIRED) 
 
Does this study involve
 
human stem cells (including iPS cells and adult 
stem cells), gametes or embryos:
No 
Yes, and requires IRB and GESCR review 
Yes, and requires GESCR review, but NOT IRB review 
4.19  
 
 
*
 
FINANCIAL INTERESTS: (REQUIRED) Do you or any other responsible personnel (or the spouse, 
 
 
registered domestic partner and/or dependent children thereof) have financial interests related to 
 
this study:
  Yes  
  No
5.0
 Funding

5.1  
 
* FEDERAL FUNDING: (REQUIRED) Is this study currently supported in whole or in part by Federal 
funding, 
, OR has it received 
 Federal funding in the past:
even by a subcontract
ANY
 Yes  
 No
5.2  
 
* 
Is this project linked in any way to the Department of Defense (DoD):
DoD INVOLVEMENT: 
(REQUIRED)
  Yes  
  No
5.3  
 
SPONSORS: Identify all sponsors and provide the funding details. If funding comes from a 
 
Subcontract, please list only the Prime Sponsor:
External Sponsors:
 
View 
Details
Sponsor Name
Sponsor Type
Awardee 
Institution:
Contract 
Type:
Project 
Number 
UCSF 
RAS 
System 
Award 
Number 
("A" + 
6 
digits) 
NIH Natl Human 
Genome Research 
Inst. 
01 
UCSF 
Grant 
 
 
Sponsor Name:
NIH Natl Human Genome Research Inst. 
Sponsor Type:
01 
Sponsor Role:
Funding
CFDA Number:
 
Grant/Contract Number:
CSER2 
Awardee Institution::
UCSF 
Is Institution the Primary 
Grant Holder:
Yes 
Contract Type:
Grant 
Project Number:
 
UCSF RAS System Award 
Number ("A" + 6 digits):
 
Grant Number for Studies Not 
Funded thru UCSF:
 
Grant Title:
 
PI Name:
(If PI is not the same as 
identified on the study.)
 
Explain Any Significant 
Discrepancy:
 
Other Funding Sources and Unfunded Research - Gift, Program, 
Departmental or other Internal Funding (check all that apply):
Funded by gift (specify source below)
Funded by UCSF or UC-wide program (specify source below)
Specific departmental funding (specify source below)

Unfunded (miscellaneous departmental funding)
Unfunded student project
6.0
 Sites, Programs, Resources, and External IRB Review
6.1    
  
 (check all that apply): 
 UCSF AND AFFILIATED SITES
*
(REQUIRED)  
UCSF Benioff Children's Hospital Oakland (BCHO)
UCSF Cancer Center Berkeley
UCSF Cancer Center San Mateo
UCSF China Basin clinics and facilities
UCSF Helen Diller Family Comprehensive Cancer Center
UCSF Langley Porter Psychiatric Institute (LPPI)
UCSF Medical Center at Mission Bay (Benioff Children's Hospital, the Betty Irene Moore 
Women's Hospital, Bakar Cancer Hospital, or outpatient clinics)
UCSF Mount Zion
UCSF Parnassus (Moffitt-Long hospital, dental clinics or other outpatient clinics)
UCSF Other Sites (including Laurel Heights and all the other sites outside the main hospitals 
and clinics)
Fresno - UCSF Fresno OR Community Medical Center (CMC)
Gladstone Institutes
Institute on Aging (IOA)
Jewish Home
SF Dept of Public Health (DPH)
SF VA Medical Center (SF VAMC)
Vitalant (formerly Blood Centers of the Pacific and Blood Systems Research Institute)
Zuckerberg San Francisco General (ZSFG)
You are required to obtain additional 
Research involving ZSFG: 
approvals from the ZSFG Dean's Office. Download the ZSFG Protocol 
 and submit the completed form to the 
Application Form
ZSFG Dean's Office.
We rely on the Community Medical Center IRB for all research at 
the UCSF Fresno campus and Community Medical Center. Check 
'Yes' to relying on an external IRB in 6.10 below. 
6.2  
At what locations will study visits and activities occur:
LOCATIONS: 
Recruitment, consent and results provision will take place at clinic outpatient appointments as 
part of standard healthcare and also as part of inpatient services. We will offer this study at 
Benioff Children's Hospital Mission bay, Benioff Children's Hospital Oakland and Zuckerberg San 
Francisco General Hospital, and UCSF Fresno/Community Medical Center.
6.3  
Will any study procedures or tests be conducted off-site by non-UCSF 
OFF-SITE PROCEDURES: 
personnel:
  Yes  
  No
6.4  RESEARCH PROGRAMS: Check any UCSF research programs this study is associated with:
Cancer Center
Center for AIDS Prevention Sciences (CAPS)

Global Health Sciences
Immune Tolerance Network (ITN)
Neurosciences Clinical Research Unit (NCRU)
Osher Center
Positive Health Program
6.5  * CTSI CRS SERVICES: (REQUIRED) Will this study be carried out at one of the UCSF Clinical Research 
 units or utilize 
:
Services (CRS)
CRS services
 Yes  
 No
 can be found at:
The CRS budget request form
 https://crs.ucsf.edu
/sites/g/files/tkssra726/f/CRS%20Budget%20Request%
. Follow the 
 
20Form_Final_8.14.20%20Restricted%20Version.docx
instructions on the form to submit.
6.6  * MULTI-CENTER TRIAL: (REQUIRED) Is this a multi-center or multi-site research trial:
By 
' we mean a study where the protocol is developed 
'multi-center trial
by an lead investigator, an industry sponsor, consortium, a disease-group, 
etc.,and multiple sites across the nation or in different countries participate 
in the trial. The local sites do not have any control over the design of the 
protocol.
  Yes  
  No
6.8  OTHER SITE TYPES: Check all the other types of sites not affiliated with UCSF with which you are 
cooperating or collaborating on this project:
Do NOT check any boxes below if this is a multi-center clinical 
trial, UCSF is just one of the sites, and neither UCSF nor one of its 
faculty-linked affiliates (SF VAMC, Gladstone, ZSFG) are the 
coordinating center.
Other UC Campus
Other institution
Other community-based site
Foreign Country
Sovereign Native American nation (e.g. Navajo Nation, Oglala Sioux Tribe, Havasupai, etc.)
6.14  * RELYING ON AN EXTERNAL IRB: (REQUIRED) Does this application include a request to rely on an 
external IRB (a central IRB (other than the NCI CIRB) or an external IRB (other UC campus, 
commercial, or institutional):
  Yes  
  No
Check 'Yes' since we rely on the Community Medical Center IRB for 
reseach that takes place in Fresno.
7.0
 Research Plan and Procedures

7.1  
Describe the hypothesis or what the study hopes to prove:
HYPOTHESIS: 
We hypothesize that next-generation sequencing studies, such as whole exome sequencing, will 
have clinical utility in patients with medical conditions that have a genetic etiology.
7.2  
List the specific aims:
AIMS: 
(1) To determine the clinical utility of whole exome sequencing in the minority 
and underserved population at 6 months after whole exome sequencing. We will 
recruit and consent up to 800 Pediatric patients and biological parents with a 
variety of indications, including intellectual disability, seizures, encephalopathy, 
metabolic disease, birth defects, neurodegerneative conditions and multiple 
congenital anomaly syndromes. We will perform whole exome seuqencng and 
provide a result(s) to the family. Results will be defined as: 
1. Results of diagnostic or medical importance in relation to the probands presenting condition or 
the reason for the test;
and, 2. Secondary or additional findings that are deemed relevant to the health of the patient or 
parents and that will be reported out to the participants and/or their primary physician. These 
secondary results can include any other result that the study team determines that is of medical 
importance and must be reported to the participant and/or their primary physician.
 
We will use the American College of Medical Genetics and Genomics published list of 59 genes 
that are considered medically actionable: http://www.nature.com/gim/journal/v19/n2/full
/gim2016190a.html
For genes that are not on this list and that may be considered actionable, the sign-out team will 
need to be in consensus that: 1) the sequence variant to be reported is ether pathogenic or likely 
pathogenic; and 2) the gene is medically actionable. If there is any controversy, a specialist in 
the relevant clinical area will be consulted regarding actionability of the gene.
After 6 months, we will see the families in follow up and assess clinical utility. 
We will recruit patients from UCSF Mission Bay, UCSF Oakland and Zuckerberg 
San Francisco General Hospital and UCSF Fresno/Community Medical Center.
 
7.3  
Briefly describe the study design (e.g., observational, interventional, randomized, placebo-
DESIGN: 
controlled, blinded, cross-over, cross-sectional, longitudinal, pharmacokinetic, etc.):  
This study aims to recruit and consent patients and biological family members who have at least 
one individual with a medical condition that is likely to have a genetic etiology. We will study the 
clinical utility of exome sequencing in underserved and underrepresented minority populations. To 
do this, we will perform whole exome sequencing as a test to generate sequence data in order to 
determine the genetic etiology of the medical condition. Families will undergo questionnaires and 
interviews to determine the clinical utility of exome sequencing for their healthcare. The medical 
providers involved in the study will also undergo questionnaires to determine if the exome 
sequencing has had clinical utility for their patient. The sequence variant data from the exome 
sequencing will be studied as part of reserach be sent to the National Institutes of Health for 
sharing in databases such as dbGAP and ClinVar, in accordance with current NIH policy. We will 
share sequence variants in the form of .vcf files and phenotype data in pedigree form that 
enables relationships between proband and other relatives to be determined. Data will be 
available for broad use that is not limited to specific diseases. 

7.4  
 Briefly provide the background and significance of this study (e.g. 
BACKGROUND AND SIGNIFICANCE:
 
why is this study needed) (space limit: one half page):
If this is a first in humans study, please summarize the safety data from 
the animal studies. For pediatric drug or device studies, please identify if 
this is the first study in pediatric populations.  
Congenital abnormalities and developmental disorders affect 3-5% of live born infants 
and children  Despite advances in both pre- and post-natal treatment, the utility of genetic 
.
testing in diagnosing the etiology underlying such conditions in order to guide management has 
been frustratingly limited. Traditional genetic testing with specific gene tests, or even gene 
panels, is diagnostic in only a small percentage of cases. Recent technological advances in next 
generation sequencing (NGS) have led to the ability to sequence and interpret the entire exome 
relatively quickly, allowing a diagnosis in 25-30% or more of cases of developmental disorders 
when other genetic tests have not yielded a result.
Although whole exome sequencing (WES) holds great promise for improved diagnosis 
leading to better clinical outcomes, challenges remain in determining how best to apply and utilize 
sequence data. Fulfilling the promise of WES also requires investigation of ELSI (ethical, legal, 
social) concerns, given skepticism in some communities that research will benefit them; economic 
considerations that ultimately determine access to and equitable use of WES; and a need to share 
clinical genetic results with families and across health care systems to enable better 
prognostication and management of rare conditions in community settings.
We propose a rogram in renatal and 
diatric enomic equencing (P EGS) at UCSF to 
P
P
Pe
G
S
3
examine the diagnostic and clinical utility of WES. P EGS will recruit and study affected 
3
individuals and their parents, including pregnancies in which the fetus has a confirmed structural 
anomaly and children with previously undiagnosed developmental disorders that are likely of 
genetic etiology. Following consent and collection of standardized phenotypic data, the families 
will undergo WES. To achieve diversity, patient ascertainment and recruitment will occur at four 
UCSF sites that serve a broad range of under-represented minorities (target of 75%) and span 
the full socio-economic spectrum, including the underserved.
 
7.5  
Briefly summarize any preliminary studies relevant to your proposed 
PRELIMINARY STUDIES: 
research 
:
(space limit: one half page)
UCSF has recently established a whole exome sequencing test and it is CLIA-approved. The 
resarchers on this protocol have had experience consenting patients and families for whole exome 
sequencing and with results provision.
 
 
7.6  
Is this a treatment study, i.e. does this study intend to provide treatment 
* TREATMENT PROTOCOL: 
to individuals with a medical or psychological condition: (REQUIRED)
  Yes  
  No
7.7  
 Does this study involve any procedures, lab tests or imaging studies that 
* BILLABLE PROCEDURES:
have a CPT code and could be billable to patients, their insurance, Medi-Cal, Medicare, or any other 
entity (answer 'Yes' even if the study is going to pay for all the procedures): (REQUIRED)
 Yes  
 No
7.8  
Types of research activities that will be carried out. Check all that 
 COMMON RESEARCH ACTIVITIES: 
*
apply and describe in more detail in the 'Procedures / Methods' section: (REQUIRED)
Interviews, questionnaires, surveys
Educational or cognitive tests
Focus groups

Social media-based research activities
Observation
Fitness tests or other exertion activities
Use of mobile health apps or other apps
Collection of data from wearable tech such as Fitbit, Apple Watch, Garmin, motion actigraphs, 
etc.)
Non-invasive imaging or testing (MRI, EEG, pulse oximetry, etc.)
Imaging procedures or treatment procedures that involve radiation (x-rays, CT scans, CT-
guided biopsies, DEXA scans, MUGA or PET scan)
Administration of contrast agent
Randomization to one intervention versus another
Use of placebo
Biopsy conducted solely for research purposes
Sham surgical procedure
None of the above
7.9  
PROCEDURES / METHODS: 
* 
(REQUIRED)
For clinical research, list all study procedures, tests and treatments 
required for this study, including when and how often they will be 
performed. If there are no clinical procedures, describe the research 
activities.
 
If some of the activities would occur even if the person were not in the 
study, as in the case of treatment or tests performed for diagnostic 
purposes, clearly differentiate between those activities that will be 
done solely for research purposes and those that are happening as 
part of routine care.
 
Examples may include:
additional scans outside standard clinical diagnosis or monitoring
additional biopsies to collect tissue for research
extra clinic visits
extra lab tests not required for clinical care
If you have a procedure table, attach it to the submission with your 
other study documents.
Recruitment and Phenotyping. We will enroll and obtain detailed phenotypic information on 800 
pediatrics subjects with a variety of conditions suggestive of a genetic etiology, including 
intellectual disability, multiple congenital anomalies, seizures and other neurological findings such 
as a movement disorder, metabolic condition, or a neurodegenerative condition. As part of this 
group, 80 patients with encephalopathy and/or multiple congenital anomalies will be enrolled 
from Pediatric Intensive Care Unit (PICUs) or Neonatal Intensive Care Units (NICUs).
A minimum of 60% of enrolled individuals will be ascertained from URMs for all of the 800 study 
subjects.
Whole exome sequencing (WES) and sequence variant interpretation. We will perform WES on the 
patient and analyze variants with our existing and well established UCSF pipeline, first 
incorporating primary gene lists in the annotation analysis and then subsequently analyzing the 
entire exome, if necessary. We will also investigate the utility of a rapid exome, with a turnaround 
time of 1 to 2 weeks, in patients with encephalopathy and/or multiple congenital anomalies 
ascertained from the PICU and NICU. Samples will also be collected from the patient's parents 
and genetic testing may be done on those samples to help interpret genetic variants identified in 
their child. The genetic testing of parental samples may be exome sequencing or may be more 
targeted testing of individual genetic variants first identified in the child. The genetic testing 
patients receive is clinical testing done through a CLIA certified labratory. 
Results delivery and follow up. We will deliver variant results to the family as part of clinical care. 
We will follow all 800 families, including those with a diagnostic, positive exome result 

(pathogenic variant(s) or likely pathogenic variant(s)) and those without a positive result 
(negative result or VUS), between 6 and 12 months after results provision to assess clinical status 
and medical care post exome sequencing.
Assessment of clinical utility. We will assess clinical utility by examining health status and 
management changes of study subjects before and after exome testing, and perform a blinded 
comparison and then statistical analysis of those with a positive sequencing result versus those 
with no result or a variant of unknown significance (VUS) from the exome sequencing. Managing 
providers will be asked to complete a survey regarding the clinical utility of exome for their 
patient. This survey will be administered in person on paper or via email. These surveys are part 
of research.
 
Procedures
1) A consent form will be given, mailed or emailed to study subjects. Subjects will also be 
provided with the UCSF Experimental Subject's Bill of Rights. During the consent process, study 
subjects will have the chance to ask questions about the study and to decide if they would like to 
join the study. Subjects that take part in this study will need to sign written consent.
2) Participants will provide a sample for genetic testing. Subjects will have a blood test at UCSF 
or go to their physician to provide us with a blood sample. A saliva sample that can be obtained 
with a kit is an alternative procedure if a subject does not wish to have venepuncture. A buccal 
swab obtained with a kit is also an alternative to venepuncture. The blood, saliva, or buccal 
swab samples will be used to obtain the genetic material (DNA) for laboratory testing. Repeat 
studies may be needed in some cases and subjects may be asked to give another blood sample in 
the future, but may choose not to donate the second sample. About two ounces of blood will be 
drawn from adults (5-7 teaspoons; around 5 ml) and one ounce (3-4 teaspoons; around 2-3 ml) 
from children depending on weight. The maximum collected for each study subject will be less 
than 3 ml/kg in neonates and children and less than 20 ml in adults. The blood will be taken by 
needle in a similar manner to other blood samples. The blood or saliva samples will be sent to the 
testing laboratory with patient identifiers, such as name, date of birth and medical record 
number, and will be stored in a locked laboratory for the entire study.
 
3) The DNA sample from the patient will undergo whole exome sequencing (WES). WES entails 
searching for genetic changes that can lead to or predispose to intellectual disability, multiple 
congenital anomalies, seizures and other neurological findings such as a movement disorder, 
metabolic condition, or a neurodegenerative condition. After the patient's sample has been 
tested, we may also test parental samples to better understand the child's genetic information. 
Parental testing may be exome sequencing or more targeted testing of individual genetic variants 
identified in the child. Patient and family history and examination data (for example, pedigrees) 
will be collected as per standard clinical practice. These data may include information on family 
members who are not enrolled in the study as per standard clinical practice. We may also obtain 
photographs of some affected individuals as per standard clinical practice. These photographs will 
be obtained with the permission of the individuals concerned. Use of recognizable photographs 
(eyes showing) will require written permission from the participant(s) or guardian concerned 
using a separate consent form that is not part of the study.
    
4) The UCSF Clinical Exome sequencing test is a test that can provide various types of results. For 
example:
We can find gene variants that are known to cause or contribute to disease.
We can find gene variants that are known 
cause or contribute to disease, meaning they are 
not to 
normal variations of the exome.
We can find gene variants that are novel and of uncertain clinical importance, meaning that we do 
not know if they cause/contribute to disease or if they are normal variations of the exome.
 
As the majority of the gene variants that we find in the course of our research will fall into the 
third category, of uncertain clinical importance, we will not routinely return results to patients or 
other patients. 
 find a gene variant that is known to cause or contribute to 
I
H o w e v e r ,  i f  w e
disease or to the patient's presentation, we will  return this result. We will only give subjects 
results about specific abnormal gene variants that we think are important to their health, and that 
confirmed by Sanger sequencing in a CLIA-certifed clinical laboratory.
will be able to be 
In this case, we will contact the study subjects by phone or email to arrange a follow up 
appointment in clinic to provide results to  families interested in learning about the results. The 
family may "opt out" of learning any of the results, and still be in the study.

If the patient and family choose to learn the results of their exome sequencing, they will be asked 
to return to Genetics clinic or to another clinic at UCSF, where
will meet with a genetic 
 they 
counselor
who will explain the findings and what they mean for 
 o r  C l i n i c a l  G e n e t i c i s t  
their health. She or he may also make recommendations for follow-up with a physician or with a 
specialist. For example, if a patient is found to have a gene variant that causes high cholesterol, 
it may be recommended to discuss this with a doctor so that he/she can monitor cholesterol 
closely. This is part of clincial care.
We will also discuss results that the study doctors think may have significant effects on patient or 
family health, but that are unrelated to the clinical indication for performing the test (secondary 
or additional findings). If the family has specified that they do not wish to learn such results, 
these will not be reported. This is part of clincial care.
 
Gene variants that are known not to cause disease or are of uncertain relevance (that may be 
normal variation) will not be reported to participants.
We will contact subjects about gene variants that are important to their health and health 
decisions; however, we expect to find very few of this type of gene variant. Subjects that are not 
contacted could still have gene variants that could cause disease or birth anomalies; not all gene 
variants that could cause disease are known and not all gene variants that could cause birth 
anomalies will be detected.
 
4) Material (DNA) taken from participants samples may be given to other researchers for studies 
on similar or other conditions. However, names or identifying details will not be given to the other 
researchers. On completion of the study, the DNA samples will continue to be stored at UCSF or 
at the institution where the work was carried out. The samples will not be given to other 
researchers outside UCSF for studies on different medical conditions.
 
We may publish a chart that shows family trees and who is affected with the condition, but we 
will not use subject identifying details. We may also publish photographs that do not show faces, 
but if we want to use photographs showing faces that are recognizable, we must first discuss this 
with participants and obtain written permission for this with a separate consent form.
 
The stored DNA samples will remain linked by code to patient and study identifiers. This is in 
order that the patient and family can be identified and informed if results are obtained that have 
direct implications for their health or medical care.
Participation in the study will take a total of about 2-3 hours over a period of 2 or more days. 
 
We will place the resulting phenotypic and genotypic data in a controlled-access database at the 
National Institutes of Health. Use of the data will not be restricted to any one condition or the 
condition for which the sample was obtained. 
 
Although the genetic testing will be performed as a clinical test in the study, we will use the 
results in the context of research, with sharing of phenotypic and genotypic information within the 
CSER2 consortium and with other researchers.
 
The UCSF Fresno/Community Medical Center, one of our study sites, will be enrolling patients 
starting in January 2020 (their own IRB was recently approved). Three of their team members 
will be adding data into our Redcap database directly and will therefore have access to our study 
identifiers. We were unable to add them to the personnel section of the study application because 
they are not UCSF employees, so we are adding them here as per Megan's instructions. They 
team members are 
Claudia Cuan, a study coordinator, 
; Leigh Ann Higa, a genetic 
CCuan2@communitymedical.org
counselor, 
; and Emily Massiello, a genetic counselor, 
LHiga@communitymedical.org
EMassiell
; Cory Airheart, a genetic counselor, cairheart@communitymedical.
o@communitymedical.org
org
 
 
7.11  
List all questionnaires, surveys, interview, or focus group guides that will be used for 
INSTRUMENTS: 
this study:
We will also analyze and describe clinical interactions and experiences across prenatal and 
pediatric clinic settings in order to understand context and document patient-provider 

1.  
2.  
3.  
4.  
5.  
6.  
7.  
interactions. These activities are part of research and are not part of clinical care. Points 1-3 
below (the video recordings of clinical interactions, ethnograhic observations and interviews are 
covered under a separate IRB protocol, 17-23118). Specifically, we wil do the following:
Conduct detailed, ethnographic observations in each clinical setting to elucidate the full 
contextual experience of families offered sequencing for a potential genetic disorder 
identified during pregnancy (the prenatal context) or during the care of their affected 
infant or child (the pediatric context).
Follow 60 families (1/3 prenatal) who 
 sequencing and conduct in-depth interviews 
accept
at two time points, targeting a sample constructed to include ancestral diversity 
(ascertained by self-reported race/ethnicity) and social/economic status (ascertained by 
insurance coverage). Physicians and genetic counselors will also video record key clinical 
interactions. Using the constant comparative method, we will compare and contrast the 
experience of families. Interviews and analysis of videos will elucidate strengths and 
limitations of communication, revealing how families—including those from diverse, 
underserved backgrounds—understand genomic sequencing, its potential outcomes, and 
its consequences.
Using semi-structured interviews, assess the reasoning and experience of 60 families who 
are offered but 
 sequencing, including the potential impact of economic and access 
refuse
issues.
Based on data gathered via the ethnography and the initial interviews, develop (in 
collaboration with the full P EGS team and with colleagues across the CSER2 “outcomes 
3
and measures” committee) and administer a 
 assessment survey tool to the full 
utility
sample of 800 families sequenced. Here we define utility to include both the parents’ 
understanding of clinical usefulness as well as their personal views about the value and 
burden of sequencing. 
In addition to the utility assessment tool, we will also administer surveys at baseline, 
return of results, and follow-up meant to provide data about patient demographics, 
information seeking habits, secondary finding preferences, quality of life, understanding of 
test results, satisfaction, etc. (see attached surveys). These surveys have been 
recommended for harmonization by the larger CSER2 consortium. These surveys will be 
administered in person, over the phone, or via mail or email.
We will also contact the providers who referred patients to the study via email and ask if 
they are willing to complete a provider survey meant to provide information about their 
experience and comfort level with genetics (this will be done once) as well as assessing 
their perception of the clinical utility of exome sequencing for the patient(s) they referred 
(this will be done twice for each patient, once after the patient's return of results 
appointment and once after their 5-7 month follow-up visit). 
We will contact executives, administrators, managers or clinicans at UCSF via email to ask 
if they are willing to complete a survey about organizational readiness to change (ORCA). 
This survey will be administered once via Redcap or on paper and will not involve any 
personal identifiers. The goal of the survey is to learn more about their views on the 
potential for implementation of clinical sequencing in healthcare systems and 
communities. The de-identified data will be pooled by the University of Washington to 
include data from the rest of the CSER2 consortium.
Attach any unpublished instruments in the 'Other Study Documents' 
section of the Initial Review Submission Packet form after 
completing the study application. Published instruments should 
NOT be attached.
7.12  
Are you drawing any blood or collecting other biosamples (e.g. tissue, 
* BIOSPECIMEN COLLECTION: 
buccal swabs, urine, saliva, hair, etc.) for analysis under this protocol and/or storage for future 
research: (REQUIRED)
 Yes  
 No
Could this study generate genetic data that may be broadly shared (e.g., submitted to 
* 
NIH in compliance with Genomic Data Sharing (GDS)/Genome-Wide Association 
 requirements): 
Studies (GWAS)
(REQUIRED)
 Yes  
 No

 
Please make sure your consent form includes the recommended 
. 
genomic data sharing language
7.13  
Briefly summarize the methods and types of analyses that will be 
STATISTICAL METHODS: 
performed:
This study will involve DNA collection from patients with intellectual disability, metabolic disease, 
encephalopathy, seizures, birth defects and multiple congenital anomaly syndromes and we do 
not anticipate the enrollment of sufficient patients to justify statistical methods of data analysis. 
However, statistical analyses relating to genetic investigations will be performed according to 
standard methods.
7.14  
List only the 5-10 most relevant references (a separate bibliography can be attached 
REFERENCES: 
 
for reference purposes if this study involves novel approaches, agents, or an emerging technology 
that the IRB may not be familiar with):
See attached bibliography.
8.0
 Biospecimen Collection and/or Bank Administration
8.1  
(check all that apply): 
TYPE OF SPECIMENS 
* 
(REQUIRED)
Blood (provide amount below)
Tissue (describe below)
Other type of biospecimen, such as sputum, cerebrospinal fluid, buccal swabs, etc. (describe 
below)
Existing/archival materials (name source below)
Briefly describe the types of biospecimens that will be collected. Provide the 
amount of blood, if applicable. For leftover/existing/archival material, 
identify the source:
We will collect venous blood from subjects who consent. In subjects who refuse venipuncture but 
who agree to a saliva sample, we will obtain a saliva sample or buccal swab using a commercial 
kit. 
8.3  
(check all that apply): 
SPECIMENS ARE: 
* 
(REQUIRED)
Leftover specimens from a clinical diagnostic or therapeutic procedure
Specimens collected for research purposes only (including extra samples taken during a 
clinical procedure)
Other
8.4  
 
: Will any specimens or portions of specimens be retained after the study is 
* FUTURE SPECIMEN USE
over for possible use in future research studies: (REQUIRED)
 Yes  
 No
8.5  
Consent for retaining specimens for future research 
SPECIMEN BANKING - CONSENT METHOD: 
* 
studies will be obtained via (check all that apply): (REQUIRED)
Specimen section within a main research study consent form
Separate specimen consent form
UCSF surgical consent form with tissue donation brochure

8.6  
Indicate where specimens will ultimately be stored: 
 SPECIMEN DESTINATION: 
*
(REQUIRED)
Indicate where specimens will be sent if they will not 
Outside Entities: 
remain at UCSF (choose at least one; check all that apply):
Cooperative group bank
NIH
Other university or collaborator
Industry sponsor
Other
N/A - all specimens will remain at UCSF
: If specimens will remain at UCSF, in what kind of 
Internal Storage
facility will they reside (choose at least one; check all that apply):
UCSF repository/bank being established under this protocol
Existing UCSF specimen repository/bank with IRB approval
National cooperative group bank housed at UCSF
Other location at UCSF (please describe)
N/A - no specimens will be retained at UCSF facilities
Please provide the name of the department, the program, and the physical 
location where the specimens will be housed. If the specimens will be 
stored in an already established bank, provide the name of the bank and its 
iRIS approval number.:
Genomic Medicine Laboratory (GML) at UCSF
8.8  
Will clinical follow-up data be linked to specimens (i.e., will medical 
CLINICAL FOLLOW-UP DATA: 
* 
record information continue to be abstracted after the specimen is collected): (REQUIRED)
 Yes  
 No
Provide duration of follow-up or 'indefinitely':
the duration of the study
8.9  
UCSF-BANKED SPECIMENS - LINKING AND SHARING OF IDENTIFIERS: 
* 
(REQUIRED)
Samples are completely de-identified before being added to the bank/repository. There is no 
way to link the specimens back to the subjects.
Samples are coded and researchers are able to link the specimens to specific subjects.
Samples are stored with direct identifiers in the repository.
Explain under what circumstances identifiers may be released with 
specimens or say 'None' if identifiers will NEVER be released with 
specimens:
Samples will not be sent with identifiers for future research.
8.10  
–
 List the identifiers that will be collected, stored, or 
UCSF-BANKED SPECIMENS  IDENTIFIERS:
linked with the specimens:
Name

Date of birth
Social Security number
Medical record number
Address
Phone number
Email address
Other dates (dates of surgery, visit dates)
8.11  
Specimens banked at UCSF may be made available to (check all that apply):
DISTRIBUTION: 
UCSF researchers
Non-UCSF researchers
Industry
None of the above - specimens will be retained and used within our own research program
8.12  
Is there a formal utilization review process for distribution of specimens:
UTILIZATION REVIEW: 
  Yes  
  No
9.0
 Drugs and Devices
9.1  
Are you 
 any drugs and/or biologics that are either 
* DRUGS AND/OR BIOLOGICS: 
STUDYING
approved or unapproved: (REQUIRED)
  Yes  
  No
If you have questions about FDA requirements for drug or device 
research, you can send an 
to request a consult.
email 
 
Note: This question is frequently answered incorrectly. If any drugs 
or biologics, approved or unapproved, are being administered under 
this protocol, you should check 'Yes' unless you are 
 sure 
absolutely
that NONE of the drugs are part of the research protocol. Tip: Ask 
the PI or the sponsor if you are not sure how to answer this 
question.
9.3  
: Are you 
 any medical devices, in vitro diagnostics, or assays that are 
* MEDICAL DEVICES
STUDYING
 
either approved or unapproved:(REQUIRED)
 Yes  
 No
If you have questions about FDA requirements for drug or device 
research, you can send an email to request a consult.
9.4  
 
 Are you requesting a Non-Significant Risk (NSR) determination for an investigational device: 
* NSR:
  
(REQUIRED)  Note: an 
 is different from an Investigational Device Exemption 
NSR determination
(IDE). Check the Help link for more guidance on what types of devices can qualify for an NSR 
 
determination.
 Yes  
 No

Explain why the use of the device in this study poses a non-significant 
* 
risk: (REQUIRED)
-The device is not intended as an implant and does not present a potential for serious risk to the 
health, safety, or welfare of a subject;
-The device (Illumina sequencer) is not purported or represented to be for a use in supporting or 
sustaining human life and does not present a potential for serious risk to the health, safety, or 
welfare of a subject;
-The device is not for a use of substantial importance in diagnosing, curing, mitigating, or 
treating disease, or otherwise preventing impairment of human health and does not present a 
potential for serious risk to the health, safety, or welfare of a subject; and
-The device otherwise does not present a potential for serious risk to the health, safety, or 
welfare of a subject.
Whole exome sequencing (WES) has been increasingly incorporated into laboratory genetic 
testing at academic and commercial laboratories. WES is aimed at detecting pathogenic 
sequence variants in patients with suspected genetic conditions and has become part of routine 
practice by Medical Geneticists, as well as an increasing number of clinicians from other medical 
specialties. Large case series from clinical laboratories (>2,800 patients) have confirmed the 
clinical validity of WES in the diagnosis of rare genetic diseases [1, 2]. Among subpopulations of 
patients, e.g. children with nervous system dysfunction, such as developmental delay, the 
diagnostic yield has been found to be as high as 41% [2]. In the Deciphering Developmental 
Disorders Study, which recruited >1,000 children with severe undiagnosed developmental 
disorders, WES combined with copy number analysis identified likely pathogenic variants in 28% 
of children [3]. These diagnostic yields are unprecedented and are not achievable with other 
testing strategies.
 
The purpose of WES is to identify an underlying etiology in patients with features suggestive of a 
genetic disorder, but without features diagnostic of a particular condition. Sequencing enables 
comprehensive screening that is not feasible with sequential single gene testing or  gene panel 
testing. For individuals with rare genetic diseases, WES has proven invaluable in establishing a 
diagnosis, determining recurrence risk for patients and other family members, understanding 
prognosis, guiding therapies and health surveillance.
 
WES sequences the entire protein-coding region of the human genome in order to identify 
disease-causing variants. In the UCSF clinical exome test, blood or tissue is collected from a 
patient and his/her biologic parents. DNA libraries are prepared from each individual by 
capturing the exome (approximately 1-2% of an individual’s entire genetic content). Libraries 
are then sequenced using Next Generation Sequencing (NGS) technologies. The aim of WES is to 
sequence the exome of each individual to a sufficient depth to detect variants; this requires tens 
of millions of 100 base pair sequences. The sequencing data is aligned to a reference genome 
and variants that differ from the reference are identified.  Among the ~30,000-60,000 variants 
identified for each individual, filtering is performed to identify candidate variants that might be 
disease-causing and to filter out variants that are common in the healthy population and that are 
not predicted to alter protein function in the cell, or that occur in highly variable regions of DNA. 
Comparisons made between sequence variants in the proband and his/her parents are used to 
investigate different models of inheritance based on fundamental principles of Mendelian 
genetics. Ultimately, a focused list of variants is then reviewed for possible pathogenicity by 
experts in genetics, molecular pathology, and clinical medicine. 
 
The UCSF Exome is designed to detect single nucleotide variants (SNVs). It may also detect 
small insertions or deletions (INDELs, typically <10bp). It is not designed to detect large 
insertions, large deletions, or structural rearrangements. Although on average, the vast majority 
of the exome will be covered by this test (99.6% at >10x during the validation), portions of the 
exome will be poorly covered in each test (which may include whole genes, select exons of 
genes or small regions of exons). Poor coverage may result from poor/absent capture during 
library preparation, difficulty in sequencing, or regions that are difficult to align to the reference 
sequence.  Identification and interpretation of sequence variants is also limited by available 
databases and publications that provide the information for filtering, manual curation and 
interpretation of variants. Although the assay performed with high sensitivity and specificity 
during the validation process (see below), false positive or false negative results are possible, as 
for any test. False positive calls will be identified and eliminated by confirmatory Sanger 
sequencing.  False negative results will also be investigated by Sanger sequencing in cases 
where there is a strong clinical suspicion for a gene of interest, such as an inherited condition 
with autosomal recessive inheritance, where the patient’s phenotype matches the molecular 
genetic diagnosis, but a variant in just one allele was detected. Sanger sequencing uses custom-

designed primers, PCR amplification, and resolution using the Life Technologies 3500 capillary 
electrophoresis instrument.  
 
Points to consider for IDE exempt device status for studies #17-22504 and 17-22420 
based on Option C, Category 2 considerations: 
The UCSF Genomic Medicine Initiative is currently undertaking two parallel studies to explore the 
clinical utility of whole exome sequencing in diverse patient populations including those in the 
pediatric and prenatal milieus. Specifically, IRB study #17-22504 Program in Prenatal and 
) and study #17-
Pediatric Genomic Sequencing (P3EGS
22420 The Clinical Utility of Prenatal 
. These are investigator initiated studies and all study participants will 
Whole Exome Sequencing
be identified, counseled and consented by clinical geneticists or genetic counselors associated 
with the study.
 
Genetic counseling will be part of the informed consent process for all potential participants, in 
order to mitigate risk.  Counseling will be offered by either a Certified Genetic Counselor, a 
Board-Certified or Board Eligible Clinical Geneticist, or in some cases both. This counseling will 
include a detailed discussion of the benefits, limits and risks to the primary study participant and 
their families from undergoing whole exome sequencing, as outlined in the respective patient 
consent forms. Additionally, for those that elect to pursue WES, a clinical geneticist or genetic 
counselor will review the WES results and discuss appropriate follow-up and management with 
the family.
 
To assure that our genetic counseling practices are understood by the diverse population that 
will participate in this study, we have developed a formal community engagement process that is 
described in the application.  Following the initial engagement, several community members will 
be appointed to our Ethics Advisory Board for the P3EGS study.  The board will meet regularly to 
address issues that might arise.  The board will also review all materials developed for 
recruitment and will offer advice on the informed consent process.  All of our materials will be 
translated into Spanish.  Certified interpreters will be used for other, less common language 
groups.   Finally, one of our project Co-Investigators, Galen Joseph, is nationally known for her 
pioneering work on genetic counseling in diverse populations and across language barriers.  Her 
work has paved the way for counseling innovations that improve the understanding of low 
literacy groups.  She will be part of the Ethics Advisory Board.
 
These studies should both be considered IDE exempt device studies under Category 2 
considerations for the reasons articulated below.
 
We are using WES to identify a unifying genetic cause for developmental delays/intellectual 
disability, congenital anomalies, seizures, encephalopathy or neuromuscular conditions. The WES 
is therefore being used as a diagnostic test.
Samples obtained for WES will be collected by either blood draw or saliva sample for the 
pediatric patients (study #17-22504) and all parent participants. We may also use DNA derived 
from a specimen that was previously obtained for other diagnostic purposes, including 
microarray analysis. For participants undergoing WES in the prenatal study (study #17-22420), 
DNA samples submitted for WES will be derived from a previously obtained specimen -- an entry 
criterion for the prenatal study is that all participants will have previously undergone prenatal 
genetic diagnosis by established methods of karyotyping and/or chromosomal microarray 
analysis.
No invasive procedures other than a simple blood draw are connected with the use of the WES 
test in either study.
The testing does not introduce energy into study participants. All imaging performed for 
inclusion criteria in the prenatal arm is clinically indicated and will have been completed prior to 
enrollment by the patient’s clinical provider(s).  Magnetic resonance imaging (MRI) or 
computerized tomography (CT) scan will not be used for diagnosis of a fetal anomaly as part of 
this study.
To mitigate the risk for a false positive result from the WES pipeline, all sequence variants with 
clinical relevance that will be reported will be confirmed by Sanger sequencing, a test that is the 
current laboratory “gold standard” for variant detection. We anticipate that WES in both the 
pediatric and prenatal studies will yield an underlying genetic cause in approximately 30-40% of 
patients tested. The majority of study participants will therefore have non-informative test 
results. When appropriate, Sanger sequencing may be applied to investigate genes in which 
there is high clinical suspicion for sequence variants that may have been missed by WES.
Any necessary language for labeling will be applied.
Attach any documentation you have from the manufacturer and/or 
FDA to support this determination.

9.5  
List the medical devices or in vitro diagnostics to be studied or used. In the device 
LIST THE DEVICES: 
details screen you will be asked questions such as:
Whether the device is FDA approved or investigational
Medicare device category
If the device will be provided at no cost
If an IDE is necessary, the IDE number, and who holds the IDE
Risk category of the device
FDA status of the device
Please see the 
 for more details about the use of devices in research, including the 
UCSF IRB website
  
Investigator Checklist for Significant Risk, Non-Significant Risk, and/or IDE Exempt Device Studies  
 If the sponsor’s protocol does not list the IDE number, you must submit 
Verification of IDE numbers:
documentation from the sponsor or FDA identifying the IDE number for this study. Attach this 
  
documentation in the Other Study Documents section of the Initial Review Submission Packet.  If 
you have any correspondence from the FDA or sponsor regarding this device, 
 
please attach it to the application.  
View 
Details
Device Name
Is the Device 
FDA Approved
Is this a new 
device or a new 
use of an already 
approved device
IDE Number
Illumina Sequencer 
No 
Yes 
 
Manufacturer/Supplier of 
Device
Illumina 
Medicare Category
A
B
Where will the Devices Be 
Stored
Parnassus 
Will Devices be supplied at no 
Cost
Yes 
Is this a HUD (HDE)
No 
HDE Number
 
Is the Device FDA Approved
No 
Is this a new device or a new 
use of an already approved 
device
Yes  
Is an IDE necessary
No  
IDE Number
 
Who holds the IDE
N/A  
IDE details
These studies should both be considered IDE exempt device 
studies under Category 2 considerations.  
In the opinion of the sponsor, 
select the level of risk 
associated with this device
No Significant Risk  
9.6  
Is this an expanded access or compassionate use protocol, meaning the 
* EXPANDED ACCESS: 
primary purpose is to diagnose, monitor or treat a patient's condition, rather than the collection of 
safety and efficacy data of the experimental agent: (REQUIRED)
  Yes  
  No
10.0
 Sample Size and Eligibility Criteria

10.1  
 
How many people will you enroll:
ENROLLMENT TARGET: 
up to 800 families
 If there are multiple participant groups, indicate how many people will be 
in each group:
Our enrollment goals for patients include up to 800 probands and up to 1700 biological parents or 
other family members.
 
There are no power calculations associated with this study. We chose 800 patients to maximize 
enrollment of pediatric patients with likely genetic diagnoses within the cost restraints of the 
grant. Patients will be enrolled with one or two biological parents, and in some cases with affected 
siblings as well.
 
We also estimate enrolling approximately 25 physicians who have referred patients to the study. 
These referring physicians, most of whom are study investigators, will be asked to complete 
surveys primarily meant to assess the clinical utility of exome sequencing for the patients they 
referred and to provide limited information about their own background.
 
We estimate enrolling approximately 10 administrators or clinicians at UCSF to complete the 
ORCA questionnaire.
10.3  
Explain how and why the number of people was chosen. For multi-site 
SAMPLE SIZE JUSTIFICATION: 
studies, this is referring to the number that will be enrolled across all sites:
Our enrollment goals for patients include up to 800 probands and up to 1700 biological parents or 
other family members.
 
There are no power calculations associated with this study. We chose 800 patients to maximize 
enrollment of pediatric patients with likely genetic diagnoses within the cost restraints of the 
grant. Patients will be enrolled with one or two biological parents, and in some cases with affected 
siblings as well.
 
We also estimate enrolling approximately 25 physicians who have referred patients to the study. 
These referring physicians, most of whom are study investigators, will be asked to complete 
surveys primarily meant to assess the clinical utility of exome sequencing for the patients they 
referred and to provide limited information about their own background.
 
We estimate enrolling approximately 10 administrators or clinicians at UCSF to complete the 
ORCA questionnaire.
10.4  
Eligible age ranges: 
* 
 AGE RANGE: 
PARTICIPANT
(REQUIRED)
0-6 years
7-12 years
13-17 years
18-64 years
65+
10.5  
 Data will be collected from or about the following types of people (check all 
STUDY POPULATIONS:
* 
 
that apply): (REQUIRED)
Inpatients
Outpatients
Family members or caregivers
Providers
People who have a condition but who are not being seen as patients
Healthy volunteers
Students
Staff of UCSF or affiliated institutions

None of the above
10.6  
Check the populations that may be enrolled: 
SPECIAL SUBJECT GROUPS: 
* 
(REQUIRED)
Children / Minors
Adult subjects unable to consent for themselves
Adult subjects unable to consent for themselves (emergency setting)
Subjects with diminished capacity to consent
Subjects unable to read, speak or understand English
Pregnant women
Fetuses
Neonates
Prisoners
Economically or educationally disadvantaged persons
None of the above
If not already addressed in the Background and Significance questions in 
the Research Plan section or elsewhere, explain why it is appropriate to 
include the types of subjects checked above in this particular study:
We would plan to include minors or adults who are mentally impaired and persons who are unable 
to give consent for themselves in this study. We will use impartial observers (a physician who is 
not a study investigator) to determine the ability of a study subject to give consent. We will use 
the assent process for persons who are judged to have mental competence above that of an 
average seven-year old as judged by an impartial observer. For the consent for minors, an assent 
form and a guardian consent form have been prepared. If the study subject has cognitive 
impairment, we will use a surrogate for the consent process according to the guidelines of the 
University of California for consent in a non-emergency setting. Prior to consent, we will explain 
the nature of the research and the risks and benefits of surrogate participation to both the 
subject and the surrogate. The alternatives to participation will also be explained. For the 
surrogate, we will try to ensure that the surrogate has adequate knowledge of the study, that 
they are familiar with the subject's degree of mental impairment and that they are willing to 
serve as the substitute decision maker. We will ask the surrogate to make the decision about 
research participation based on the subject's known preferences or based upon a judgement of 
what the subject's preferences would be. The surrogate must also complete a self-certification 
form.
We would plan to include pregnant women in this study. The pregnant women will be involved in 
the study in the same way that non-pregnant women will be involved in the study, but we would 
not study the unborn children of the pregnant women.
We will offer the study and participation in the study to every ethnic population group. We will 
provide consent forms that are translated for families who speak Spanish, but for other 
languages, we will use certified translators for those who speak other languages rather than 
English, as a first language.
 
The providers who refer patients to our study will be asked if they are willing to participate in 
provider surveys to assess the clinical utility of exome sequencing for the patient(s) they referred 
and characterize their experience with and comfort level with genetics. As most of our referring 
providers are study investigators, the majority of those participating will also be study 
investigators. There may also be other non-investigator UCSF/SFGH/BCHO physicians who refer 
patients and whom we ask to participate.
 
Administrators and clinical staff who are involved with the research study may be asked to fill out 
a survey. The survey is regarding organizational readiness to change (ORCA). The ORCA is 
designed to evaluate the potential for healthcare systems, hospitals, and clinics to adapt when 
new healthcare practices and clinical services are introduced. We will ask six to ten executives, 
administrators, managers, or clinicians at each site participating in your project. Respondents of 
interest include hospital or healthcare system executives, administrators, and managers in roles 
such as chief executive officer, chief operating officer, chief of staff, vice president of patient care, 
chief financial officer, service chief, director, manager, supervisor, or clinician. Our principal 
investigators will identify respondants who are qualified to answer these questions.

1.  
2.  
3.  
4.  
5.  
1.  
2.  
3.  
Describe the additional safeguards that have been included in the study to 
protect the rights and welfare of these subjects and minimize coercion or 
undue influence:
Here are some examples:
evaluating capacity to consent for individuals who may be decisionally 
impaired (specify how)
calibrating payment amounts to be non-coercive for the financially 
disadvantaged
conducting more in-depth evaluations of subjects’ understanding of 
the study and the voluntary nature of participation
involving advocates in the consent process
More information and other safeguards are described here: Vulnerable 
 and 
.
Subject Populations
Recruiting Staff and Students
Patients will have study alternatives explained to them and have the right to refuse to participate. 
They also have the right to withdraw and have their samples destroyed at any time.
 
Providers also have the right to decline to participate in the surveys.
 
Administrators and other study staff and clinicians also have the right to decline to participate in 
the surveys.
10.7  
 Briefly describe the population(s) that will be involved in this study. Include 
INCLUSION CRITERIA: 
anyone that data will be collected from or about (e.g. patients, healthy controls, caregivers, 
providers, administrators, students, parents, family members, etc.):
 
For patients:
Presenting clinical features suggestive of a genetic etiology, including ID, seizures, 
multiple congenital anomalies, metabolic conditions, and neurodegenerative conditions or 
idiopathic CP; 80 of these patients will have encephalopathy or multiple congenital 
anomalies so that they may benefit from rapid exome sequencing in the PICU or NICU. A 
total of 800 will be recruited, of which a minimum of 60% will be from URMs.
A minimum of one biological parent is available and willing to provide a biospecimen for 
WES, with a preference for two available parents. At least one parent consenting to WES 
of the child. 
Pediatric patients must have had at least one prior genetics appointment or evaluation
Patients must have had a single nucleotide polymorphism (SNP) array or oligonucleotide 
array that did not provide a diagnosis, unless the principal investigator exempts the 
patient from this requirement due to having a condition for which array has a low 
diagnostic yield.
Proband must be under 26yo at time of enrollment.
 
For physicians:
1. We will enroll physicians in the study and ask them to complete surveys if they have referred 
at least one patient to the P3EGS study.
10.8  
 List any exclusion criteria (e.g. reasons why someone would not be included 
EXCLUSION CRITERIA:
in the study):
For patients:
Prior WES performed for a clinical or research indication
Lack of phenotypic indication of a likely underlying genetic etiology
Both biological parents are unavailable.
For physicians:
     1. They have not referred a patient to P3EGS.

10.9  
Do any study activities take place on any 
* RESEARCH CONDUCTED ON PATIENT CARE WARDS: 
patient care units including inpatient wards, peri- or post-operative care units, operating rooms, or 
 
in the Emergency Department at UCSF Health medical facilities: (REQUIRED)
  Yes  
  No
10.10  
 
 Will you be enrolling any babies who are admitted to the 
* INTENSIVE CARE NURSERY (ICN):
Intensive Care Nursery (ICN) (this includes critically ill babies as well as lower acuity patients who 
need overnight monitoring and support): (REQUIRED)
 Yes  
 No
Research projects recruiting in the ICN involve Screening Services provided 
by the CTSI CRS. This service is provided at no cost but they still need you 
to complete the 
In the form, under 
. 
CRS Budget Request Form
'Requested CRS Resources,' NCRC Coordinator, please check the box for 
'Screening.' If you are requesting any other CRS services, complete the 
remainder of the form to receive a budget estimate. Please contact the 
Nurse Manager, Kim Johnston via email or phone at 415-353-9672 
to review your needs for this study.
 
10.11  
Does your protocol or study involve any of the following patient 
EMERGENCY DEPARTMENT: 
* 
related activities in the emergency department (e.g. subject identification, recruitment, consent, 
blood draws, specimen retrieval, involvement of ED staff (nursing, tech, and/or physician), or any 
other ED based procedures): (REQUIRED)
 
  Yes  
  No
11.0
 Inclusion of Minors in Research
11.1  
Select all the 
 that apply:
REGULATORY CATEGORIES OF RESEARCH: 
regulatory categories
No greater than minimal risk (45 CFR 46.404, 21 CFR 50.51)
Greater than minimal risk but presenting prospect of direct benefit (45 CFR 46.405, 21 CFR 
50.52)
Greater than minimal risk (though only a minor increase over minimal risk) and no prospect 
of direct benefit but likely to yield generalizable knowledge about the subjects disorder or 
condition (45 CFR 46.406, 21 CFR 50.53)
Research not otherwise approvable which presents an opportunity to understand, prevent, or 
alleviate a serious problem affecting the health or welfare of children (45 CFR 46.407, 21 CFR 
50.54)
Explain why the research in this study falls under the above category or 
categories:
The risks from venepucture and from data deposition in a shared scientific database are relatively 
small, and yet future patients may potentially benefit if a genetic cause is found for their medical 
condition.
11.2  
MINORS CONSENTING: Will this study enroll minors who can 
 (as in 
legally consent for themselves
the case of emancipated minors or minors being treated for pregnancy or drug use without their 
parents knowing). This is different from agreeing to be in the study even when their parents are the 
ones providing 'official' consent, which we refer to as 'providing assent':

Note: This is very rare and the answer is usually 'No.'
  Yes  
  No
11.3  
PARENTAL PERMISSION VS. WAIVER: Please review the 
 to see under what circumstances 
guidance
the IRB can waive parental permission.
Parental permission will be obtained
Waiver of parental permission is requested: The waiver meets the provisions for a waiver of 
consent (i.e., the research poses minimal risk, it could not practicably be carried out without 
the waiver of parental permission, AND the waiver will not adversely affect the rights and 
welfare of the minor participants (45 CFR 46.116(d))
Waiver of parental permission is requested: Parental permission is not a reasonable 
requirement to protect the minor (e.g. neglected or abused children) or parental knowledge 
of the study may endanger the health or welfare of the minor (45 CRF 46.408(c))
Provide details on the other protections that will be in place:
11.4  
 Please review the 
 to see under what circumstances the 
ASSENT OF MINORS OR WAIVER:
guidance
IRB can waive assent.
Assent of children developmentally and psychologically able to provide assent will be obtained
Waiver of assent is requested: The capability of some or all of the children is so limited that 
they cannot reasonably be consulted
Waiver of assent is requested: The research holds out a prospect of direct benefit that is 
important to the health or well-being of the children and is available only in the context of the 
research
Waiver of assent is requested: The activities involving the minor are limited to chart review or 
the something equally innocuous
Waiver of assent is requested: It is not culturally appropriate to involve the minor in the 
decision to participate (e.g. some foreign research)
11.5  
(select all that will be used):
DOCUMENTATION OF PERMISSION AND ASSENT: 
Permission form addressed to the parents
Simplified assent form addressed to the child, 7-12 years old (parents get separate form)
Assent form addressed to the child, 13 years and older (for subjects and parents)
Assent form addressed to the child, 13 years and older (parents get separate form)
Check one:
One parent's signature will be obtained 
Two parents' signatures will be obtained 
If this study is approvable under regulatory category .405 and you plan to get permission from 
only one parent, explain why you think one parent's permission is sufficient:
The only invasive procedure in this study is venepuncture, and clinical decisions regarding this 
procedure are frequently made by one parent.
11.6  
Might this study enroll wards of the state:
WARDS OF THE STATE: 
 Yes  
 No
11.7  
It is appropriate to enroll wards in this study because:
WARDS JUSTIFICATION: 

We do not anticipate that it will be common that we will enroll wards of state. However, we will 
offer study participation to all potentially affected individuals, including wards of state as 
appropriate.
12.0
 Recruitment and Consent
12.1  
Is this a competitive enrollment clinical trial? By competitive 
* COMPETITIVE ENROLLMENT: 
enrollment, we mean that sites who do not enroll participants early may not get to participate at all: 
(REQUIRED)  
  Yes  
  No
12.2  
 
What kinds of methods will be used to identify potential 
* SUBJECT IDENTIFICATION METHODS: 
participants for recruitment (check all that apply): (REQUIRED)
Review of patients' conditions, history, test results, etc. (includes patients seen in clinic, 
scheduled for surgery, a procedure, imaging, or tests, or seen in the Emergency Department 
as well as searching through medical record data for possible cohort identification)
Already approved recruitment registry
Re-contact of participants from the investigators' previous studies
Referrals from colleagues (attach the 'Dear Colleague' letter or other recruitment materials 
you will provide to colleagues)
Referrals from the community / word of mouth
Advertisements (flyers, brochures, radio or t.v. ads, posting on clinical research sites or social 
media, presentation of the study at community events/media, etc.)
Online recruiting tool (describe below)
CTSI Recruitment Services unit
Posting on UCSF Clinical Trials, ClinicalTrials.gov or other publicly available clinical trial website
Other method (describe below)
* Provide details about the subject identification methods: (REQUIRED)
We have created a brochure to hand out in clinic to explain the the study to potential participants. 
We may also mail the brochure to potential study participants who have been identified as 
candidates by study clinicians, but only after someone from the study team has discussed the 
study with the family at an in person clinic visit or over the phone. 
 
12.3  * SEARCHING OF MEDICAL RECORDS: (REQUIRED)
Whose patients are they:
Investigators' own patients or patients seen within the same practice
Patients not under the care of the investigators
How and by whom will records be accessed and searched (check all that 
apply):
Self-search in APeX or other medical records source
Self-search using UCSF's Research Cohort Selection Tool
CTSI Consultation Service Recruitment Services
UCSF Academic Research Services (ARS)
University of California Research Exchange (UC ReX)
Other method (describe below)

12.4  
How, when, and by whom will eligibility for recruitment be 
DETERMINATION OF ELIGIBILITY: 
determined:
All study activities will take place at outpatient clinic visits or inpatient consults, so that families 
will not be required to schedule additional medical visits. We anticipate that ascertainment of 
infants and children will occur most frequently in outpatient General Genetics, Neurology or 
Neurometabolic clinics or in the NICU or PICU. All patients will have had at least one previous 
outpatient or inpatient encounter with a study clinician (Geneticist or Child Neurologist) to 
establish care. These encounters prior to study entry will enable clinicians to determine if whole 
exome sequencing is an appropriate next step for patient care and tabulate the underrepresented 
minority status and socioeconomic status of the patient and family, in addition to establishing a 
therapeutic relationship with the family. All patients entering the study will also have had clinical 
genetic testing as appropriate to their presenting complaint that was achievable with their 
insurance (for example, fragile X testing for patients with ID), including CMA or a single 
nucleotide polymorphism (SNP) array to exclude clinically significant copy number variants prior 
to study entry.
 
Outpatients will be referred to the study by a clinician. Inpatients may be referred by clinicians or 
may be identified by the study team through chart review. In the latter situation, the study team 
(genetic counselor, study coordinator, principal investigator), will do periodic chart review of the 
patient lists in the ICN and PICU to identify eligible patients. Once identified, the study team will 
contact the patient's care team to ask for permission to approach the family. 
12.5  
Who initiates contact (check all that apply): 
INITIATION OF CONTACT: 
* 
(REQUIRED)
Investigators/study team
UCSF recruitment unit (e.g. CTSI Consultation Services)
Potential participant
Other (explain below)
12.6  
 (check all that apply): 
HOW IS CONTACT INITIATED:
* 
(REQUIRED)
In person
Phone
Letter / email
Website or app
Other (explain below)
Attach the telephone recruitment script in the Other Study 
Documents section of the Initial Review Submission Packet Form. If 
potential participants will initiate contact, attach the telephone 
screening script that will be used to provide more information about 
the study and determine if callers are eligible to participate.
12.7  
Based on the checkboxes you chose above, please provide a narrative 
RECRUITMENT PLAN: 
describing your recruitment plan. We want to know:
Who is conducting the search for potential participants, and how?
How are potential subjects being approached for recruitment? By whom, and when?
If there will be more than one participant group (e.g. patients, healthy controls, caregivers, family 
members, providers, etc.), provide details about the recruitment plans for each group. 
(Recommended length - 100-250 words)
The key clinicians from each of our study sites will ascertain and recruit patients together with 
dedicated genetic counselors and research assistants who will be located on-site.
 
We are also utilizing phone and telehealth to recruit.
 

The providers who refer patients to the study will also be asked to participate in provider surveys. 
They will be asked via email after they have reffered a patient who has been enrolled. The 
majority of the referring providers are study investigators.
   
12.8  
How will permission to participate (i.e., informed consent) be obtained from 
CONSENT METHODS: 
* 
each potential participant. If there will be multiple groups and different plans for consenting each, 
  
check all that apply. See the orange Help bubble to the right for more detailed guidance.  
 
Participants will (check all that apply): (REQUIRED)
Sign a paper consent form at the end of the consent discussion (signed consent)
Sign an electronic consent form using DocuSign (signed consent)
Provide online consent through an app, a website, or a survey tool such as Qualtrics or 
REDCap (waiver of signed consent)
Be told about the study and be given a handout/information sheet and be asked if they agree 
to participate (verbal consent - waiver of signed consent)
Complete the study activities and turn in materials, as in the case of a completed survey that 
is placed in a drop box or mailed to the study team (implied consent - waiver of signed 
consent)
Not be able to provide consent and will have a family member consent for them, as in the 
case of a critically ill or unconscious patient (surrogate consent)
Not be able to provide consent (emergency waiver of consent - allowed for minimal risk 
research or greater than minimal risk research with an approved community consultation plan)
Not know about the study, as in the case of chart reviews or observations of public behavior 
(waiver of consent)
Other method (describe below)
Attach your consent form, information sheet, or electronic consent 
text in the Informed Consent Documents section of the Initial 
Review Submission Packet Form.
12.9  
Describe the process for obtaining informed consent, including details such as 
CONSENT PROCESS: 
* 
who will have the consent discussion and when participants will be asked to sign the consent form in 
relation to finding out about the study: (REQUIRED)   We encourage researchers to review our 
.
guidance on obtaining and documenting informed consent
If there are multiple groups being consented differently, provide details about the consent 
process for each group.
If you are relying on 
, provide details about how that will happen.
verbal or implied consent
For studies using online recruitment and consent or consent via mail, provide details here.
Consent from patients will be obtained by study investigators. An explanation of the study and 
consent procedure together with the consent forms and the UCSF Experimental Subject's Bill of 
Rights will be provided by the study investigators to the patient and family when they are first 
approached. If the patient and family need more time to consider the research, another meeting 
for consent will be scheduled if the family agrees to this. The consent forms will then be signed at 
the second meeting. If the family is comfortable with the study, they may sign the consent forms 
and return them to the study investigator after the initial or second approach. It is anticipated 
that some families may not choose to retain the forms after the first approach, and that new 
consent forms may be needed for a second approach if they agree. If siblings under the age of 18 
are also asked to participate in the study, parents will be asked to sign a separate consent form 
fpr each child.
 
Verbal consent for the ethnographical observations will take place in advance of the results 
session, either in person at the time of the family consent or by telephone. Before results are 
discussed, the study investigator in contact with the family will ask them if someone from 
the study team can observe and/or videorecord the results visit or phone call. They will also ask if 
the family would be willing to be interviewed about their experience of having WES 
testing.  Choosing yes or no will not affect the family’s medical care, or participation in the rest of 
this study.
 

Consent from the referring providers will be implicit if they agree to return the surveys that are 
emailed to them. We have requested a waiver of documentation of consent and have attached 
the email we plan to send to the providers.
 
Consent from the administrators, managers, etc. who will answer the ORCA questionnaire will be 
implicit if they agree to return the surveys that are emailed to them. We have requested a waiver 
of documentation of consent and have attached the email we plan to send to the providers.
 
 
 
 It is important that the people obtaining consent are qualified to do so. 
*
Briefly describe the training and experience these individuals have in 
obtaining informed consent: (REQUIRED)
Patient informed consent will be obtained by trained, licenced genetic counselors and/or medical 
geneticists with extensive exerpience obtaining informed consent for exome sequencing and 
research participation.
12.10  
Indicate how the study team will assess and enhance the subjects' 
CONSENT COMPREHENSION: 
* 
understanding of study procedures, risks, and benefits prior to signing the consent form (check all 
that apply): (REQUIRED)   Tip: Review the Consent Comprehension - Learning Notes in the Help 
bubble at the right for specific questions that can be asked to assess comprehension, consider 
using the UCSF Decision-Making Capacity Assesment Tool, and review our guidance on obtaining 
written or verbal informed consent for more detail on how to conduct the assessment.
The study team will engage the potential participant in a dialogue, using open-ended 
questions about the nature of the study or the experimental treatment, the risks and benefits 
of participating, and the voluntary nature of participation
Potential participants will be asked or shown a series of questions to assess their 
understanding of the study purpose, procedures, risks and benefits, as well as the voluntary 
nature of participation (especially appropriate when the consent process happens online or 
through a mobile health app)
Other method (describe below):
Provide details of the other approaches that will be used, if using another 
method to assess comprehension:
We will provide study participants with the opportunity to ask questions and check their 
comprehension of a few key facts by asking them about their understanding of the study.
12.12  
: Indicate which 
 you will use to consent non-English 
NON-ENGLISH CONSENT METHOD
* 
method(s)
 
speaking subjects: (REQUIRED)
Preferred Method—Consent form and other study documents will be available in the subject’s 
primary language Personnel able to discuss participation in the patient’s language will be 
present for the consent process.
Short-Form—A qualified interpreter will translate the consent form verbally, and subjects will 
be given the Experimental Subject’s Bill of Rights in their primary language, following 
instructions in Those Who do not Read, Speak or Understand English for required witnessing 
and signatures
Explain how you will maintain the ability to communicate with non-English 
* 
speakers throughout their participation in the study: (REQUIRED)
We will use qualified interpreters from Language Line Solutions and/or in-person interpreters 
based at the various recruitment sites.
12.13  
Select the regulatory category under which 
* WAIVER OF DOCUMENTATION OF SIGNED CONSENT: 
the IRB may waive the requirement to obtain 
consent for this study:
signed 
The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 

will be asked whether they want documentation linking them with the research. 46.117(c) 
(1)  
The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
46.117(c) (2)  
12.14  
What is the estimated time commitment for participants (per visit and in total):
TIME: 
    The time required for participation in this study for patients includes reading of the consent 
form, a discussion to obtain consent and for questions (up to 1-2 hours) and sample collection 
(up to 30 minutes). The study will also include follow up visits at 3 and 6-12 months after whole 
exome sequencing to assess clinical utility. 
 
For referring providers who agree to participate in our provider survey it will take approximately 
10-15 min per patient referred.
IMPORTANT TIP: Ensure this information is consistent with the 
information provided in the consent form.
13.0
 Waiver of Consent/Authorization for Recruitment 
Purposes
This section is required when medical records may be reviewed to 
determine eligibility for recruitment.
13.1  
Study personnel need to access 
* PRACTICABILITY OF OBTAINING CONSENT PRIOR TO ACCESS: 
protected health information (PHI) during the recruitment process and it is not practicable to obtain 
informed consent until potential subjects have been identified: (REQUIRED)
Yes 
If 
, a waiver of consent/authorization is NOT needed.
no
13.2  
 
A waiver for screening of health records to identify potential subjects poses no 
* RISK TO PRIVACY: 
more than minimal risk to privacy for participants:
Yes 
If 
, a waiver of authorization can NOT be granted.
no
13.3  
Screening health records prior to obtaining consent will not adversely affect 
* RIGHTS/WELFARE: 
subjects' rights and welfare:
Yes 
If 
, a waiver of authorization can NOT be granted.
no
13.4  
Check all the identifiers that will be collected prior to obtaining informed consent:
* IDENTIFIERS: 
Names
Dates
Postal addresses
Phone numbers
Fax numbers
Email addresses

Social Security Numbers*
Medical record numbers
Health plan numbers
Account numbers
License or certificate numbers
Vehicle ID numbers
Device identifiers or serial numbers
Web URLs
IP address numbers
Biometric identifiers
Facial photos or other identifiable images
Any other unique identifier
None
Note: HIPAA rules require that you collect the minimum necessary.
13.5  
 
Describe any health information that will be collected prior to obtaining 
* HEALTH INFORMATION: 
informed consent:
Physicians referring patients to the study submit screening forms to the study team that include 
names, DOBs, MRNs, address and phone number of the patient. This information is stored 
securely in Redcap.
Note: HIPAA requires that you collect the minimum necessary.
13.6  
Describe your plan to destroy any identifiable data 
* DATA RETENTION/DESTRUCTION PLAN: 
collected to determine eligibility for recruitment. This should be done at the earliest opportunity. If 
you plan to retain identifiable recruitment data, provide the justification for doing so:
Information from those who did not qualify for the study or were not enrolled in the study will be 
deleted after the conclusion of the study; if subjects consent, our consent will include HIPAA 
language that enables us to link their medical information with a study number.
14.0
 Risks and Benefits
14.1  
Check if your study involves any of these specific research-related risks 
RESEARCH-RELATED RISKS: 
to participants that may need to be disclosed in the consent form:
For interventional studies, risk that the regimen may be more harmful or less effective than 
other available interventions
Risks associated with radiation exposure for imaging studies specifically for research purposes
Risks associated with the administration of contrast agent for imaging studies
Risks associated with withholding of treatment or discontinuation of current treatment (e.g., 
washout period is required by the study protocol)
For randomized, placebo-controlled trials, possible temporary or permanent health 
consequences from the deprivation of effective therapies during the placebo administration 
period
For studies involving a sham surgical procedure, the risk that participants may experience 
increased morbidity without the possibility of benefit
Risks associated with modification or extension of a surgical procedure primarily for research 
purposes (e.g. risks associated with prolonging anesthesia, time in the operating room, etc.)
Risk of pain or physical discomfort caused by the research intervention
Possible personal discomfort due to sensitive topics (stress, embarassment, trauma)
14.2  
Describe any anticipated risks and discomforts not listed above: 
RISKS: 
* 
(REQUIRED)

The physical risks from blood drawing or obtaining saliva are very small. There is usually a short-
lived pain with a needle stick for a blood draw and there may be bruises at the place of the 
needle stick. There is also a very small chance of infection, excess bleeding or fainting (feeling 
lightheaded) from blood drawing. The risk involved will not be any different from that experienced 
during any clinical blood test. The amount of blood taken will not be enough to cause anemia. 
Saliva sample collection and buccal swab collection are non-invasive and don't pose any 
significant risks.
 
In some genetic studies, emotional and psychological risks are also possible. Some people are 
concerned that research about genetic causes of illness may give information that is not only 
about themselves, but also about their relatives and other groups of people who are like them. 
We will not provide information about the health of participants to other family members or other 
people, apart from family members who sign consent and participate in this study, such as 
parents. Issues of adoption and paternity (biological fatherhood) may be discovered from this 
study. We will not discuss such information with study subjects unless it has direct medical 
implications for them or their families, which is unlikely.
 
To do more powerful research, it is helpful for researchers to share information that they get from 
studying human samples by putting it into one or more scientific databases. Some of the genetic 
and health information from participants will be placed into a scientific database called "dbGaP" 
that is maintained by the National Institutes of Health. Some of the genetic and health 
information from participants may also be placed in another database called “ClinVar” that is 
maintained by the National Institutes of Health. For both databases, a researcher who wants to 
study the information must apply and be approved to use the database. Researchers with an 
approved study may be able to see and use participant information (along with that of many 
other people), but names and other identifiers (such as address or social security number) will 
not be placed into the scientific database. As genetic information is unique to study participants, 
however, there is a small chance that someone could trace it back to an individual subject. The 
risk of this happening is very small, but may grow in the future.
 
Subjects may be concerned that someone could get access to their genetic information and that it 
could be misused; for example, if genetic information suggested something serious about a 
participant's health, it could be used to make it harder for that person to get or keep a job or 
insurance. These problems may also occur if subjects disclose information themselves or agree to 
have research records released. There are laws in place that make it illegal for an employer or 
health insurance company to discriminate against an individual based on their genetic information.
 
Participation in research will involve a loss of privacy, but information about subjects will be 
handled as confidentially as possible. Participant names will not be used in any published reports 
about this study.
 
 
 
14.3  
MINIMIZING RISKS: Describe the steps you have taken to minimize the risks/discomforts to 
subjects. Examples include:
designing the study to make use of procedures involving less risk when appropriate
minimizing study procedures by taking advantage of clinical procedures conducted on the 
study participants
mitigating risks by planning special monitoring or conducting supportive interventions for the 
study
having a plan for evaluation and possible referral of subjects who report suicidal ideation
    The risks of participation in this protocol for subjects and their families are small. They include 
the risks and discomfort from venipuncture such as bruising and bleeding, light-headedness and 
syncope. The psychological risks include the disclosure of affected status and family relationships 
from the publication of clinical details at conferences or in medical journals. Attempts will be 
made to minimize these risks by publishing the minimum amount of clinical material and by 
preserving anonymity. The benefits from this protocol include the identification of genetic loci and 
causative genes for medical conditions and the sharing of variant data with other reserachers. We 
will also gain valuable insights into the clinical utility of whole exome sequencing. However, there 
may be no direct benefits to the subjects of this study.  
14.4  
Describe the resources in place to conduct this study in a way that assures protection 
RESOURCES: 
of the rights and welfare of participants:   These resources typically include appropriately trained 

and qualified personnel (in terms availability, number, expertise and experience), funding, space, 
  
equipment, and time to devote to study activities.  Depending on the nature of the research study, 
investigators should consider the proximity or availability of critical resources that may be essential 
to the safety and welfare of participants, such as
the proximity of an emergency facility for care of participant injury
availability of psychological support after participation
resources for participant communication, such as language translation services
We will minimize the effects of venipuncture by offering saliva collection to those who do not want 
a blood draw. Adverse effects of venipuncture and adverse psychological effects due to research 
participation will be reported as required to the CHR if they occur. If injury occurs from a 
procedure performed in this study, treatment will be made available. The costs of this treatment 
may be provided by the University, depending on a number of factors. UCSF does not normally 
provide any alternative form of compensation for injury. For further information about this, the 
subjects may call the office of the Committee on Human Research at (415) 476-1814 or write to 
that office at Box 0616, University of California San Francisco, San Francisco, CA 94143-0616.
 
To minimize the risk of loss of privacy to providers who particpate in the study by answering 
survey questions we will pool the responses from all four study sites (UCSF, UCSF Fresno, BCHO, 
ZSFGH). The survey does not ask for the place of employment of the provider, so this will 
increase the total number of responses and should reduce the chances that any one provider 
could be identified. We have also added a sentence into our email template about the risk of loss 
of privacy.
 
To minimize the risk of loss of privacy associated with the ORCA survey given to administrators 
and clinicians at UCSF we have made the survey anonymous--it does not ask for personal 
information from the respondent. The only information we will know about the respondent is 
which institution they are employed and answers to questions on the survey. Since the survey is 
anonymous we believe the risk is minimal.
14.5  
BENEFITS: 
* 
(REQUIRED) Note: These are the benefits that the IRB will consider during their review. 
They are not necessarily appropriate to include in the consent form.
Possible immediate and/or direct benefits to participants and society at 
large (check all that apply):
Positive health outcome (e.g. improvement of condition, relief of pain, increased mobility, 
etc.)
Closer follow-up than standard care may lead to improved outcomes or patient engagement
Health and lifestyle changes may occur as a result of participation
Knowledge may be gained about their health and health conditions
Feeling of contribution to knowledge in the health or social sciences field
The research presents a reasonable opportunity to further the understanding, prevention, or 
alleviation of a serious problem affecting the health or welfare of children
Other benefit (describe below)
None
14.6  
Explain why the risks to subjects are reasonable in relation to anticipated 
RISK TO BENEFIT RATIO: 
benefits, if any, to the participant or society:
    The risks of participation in this protocol for subjects and their relatives if they consent include:
(1) the risks and discomfort from venipuncture such as bruising and bleeding, light-headedness 
and syncope
(2) the psychological risks from the disclosure of affected status and family relationships from the 
publication of clinical details at conferences or in medical journals.
(3) The risks of subject identification following data despoition in a shared scientific database.
However, the benefits, if new genes are identified, could be substantial in terms of improved 
patient care. In addition, assessing clinical utility is also likely to be helpful for patient care.
15.0
 Confidentiality, Privacy, and Data Security

15.1  
Indicate how subject privacy will be protected:
PROTECTING PRIVACY: 
Conduct conversations about the research in a private room
Ask the subject how they wish to be communicated with – what phone numbers can be 
called, can messages be left, can they receive mail about the study at home, etc.
Take special measures to ensure that data collected about sensitive issues do not get added 
to their medical records or shared with others without the subject’s permission
Other methods (describe below)
15.2  
Do any of the instruments ask about illegal or stigmatized behavior:
SENSITIVE DATA: 
  Yes  
  No
15.3  
Could a breach of 
SIGNIFICANT CONSEQUENCES OF A LOSS OF PRIVACY OR CONFIDENTIALITY: 
privacy or confidentiality result in any significant consequences to participants, such as criminal or 
civil liability, loss of state or federal benefits, or be damaging to the participant's financial standing, 
employability, or reputation:
 Yes  
 No
Check all that apply:
Embarrassment
Criminal or civil liability
Loss of state or federal benefits
Damaging to the participant's financial standing, employability, or reputation
Potential risks to insurability (health, disability, or life insurance)
Describe the potential consequences:
Loss of privacy may result in recognition of an individual or a family, or that an individual or 
family are from a particular ethnicity or cultural group. Loss of privacy may occur from publication 
of a family pedigree or a photograph or through identification of a participant from genetic data 
deposited into a shared scientific database. This may conceivably lead to stigmatization or to 
discrimination regarding healthcare or insurance, although the chances of this happening are very 
small. We are almost always able to share papers that are being written with the family prior to 
submission to a journal so that they are comfortable with the submitted material.
 
 
15.4  
Explain any extra steps that will be taken to assure 
EXTRA CONFIDENTIALITY MEASURES: 
confidentiality and protect identifiable information from improper use and disclosure, if any:
We are almost always able to share papers that are being written with the family prior to 
submission to a journal so that they are comfortable with the submitted material. We would 
discuss modifying papers prior to submission if the family indicated that they felt uncomfortable.
15.5  
Do you anticipate that this study may collect information that State or Federal 
 REPORTABILITY: 
*
law requires to be reported to other officials, such as elder abuse, child abuse, or threat to self or 
others: (REQUIRED)
  Yes  
  No
15.6  
Will this study obtain a Certificate of Confidentiality:
CERTIFICATE OF CONFIDENTIALITY: 
 
 Yes  
 No

Please include the recommended Certificate of Confidentiality 
language in the consent form. 
15.7  
Will there be any sharing of 
 research test results 
SHARING OF RESEARCH RESULTS: 
EXPERIMENTAL
with subjects or their care providers:
 Yes  
 No
Note: This is unusual and not recommended, particularly in cases 
where the tests are carried out in a non-CLIA certified laboratory, 
the results are of unproven clinical significance, or where there are 
not known preventative strategies and/or treatments. If these are 
the most likely scenarios for your study, you should check 'No.'  
 
If you have an incidental finding of clear clinical significance, call 
the HRPP QIU at 415-476-1814 for a consult. 
Explain under what circumstances research results may be shared:
We will be providing exome sequencing results to the participants and their health care providers 
from this study. Families will decide if they wish to receive secondary findings unrelated to the 
indication for exome sequencing at the time of the consent process.
Both parents, when present as part of the biological trio, must agree to hear about secondary 
findings, or these will not be returned. These results will not be included in the medical records of 
the parents. We will not be releasing results such as APOE4 and Huntington's, as there are no 
definitive treatments available. For secondary findings that relate to adult onset disorders, we will 
report them and include them even if the child is not 18 years of age. Children may leave the 
area and not be traceable if the results are not released, and they cannot be stored without 
confidentiality risks.
 
 
 
15.9  
Study data will be: 
* HIPAA APPLICABILITY: 
(REQUIRED)
Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below)
Added to the hospital or clinical medical record
Created or collected as part of health care
Used to make health care decisions
Obtained from the subject, including interviews, questionnaires
Obtained ONLY from a foreign country or countries
Obtained ONLY from records open to the public
Obtained from existing research records
None of the above
Derived from the Integrated Data Repository (IDR) or The Health Record Data Service 
(THREDS) at SFGH
In addition to signing a consent form, each subject will have to sign 
 
the UCSF Research Subject Authorization Form (HIPAA Form). 
Upload the HIPAA Authorization Form in the Other Study 
Documents section of the Initial Review Submission Packet Form. 
Failure to have patients sign the HIPAA Authorization is one of the 
 Please call 
most common findings from QIU Routine Site Visits.
the IRB office at 415-476-1814 if you have questions about HIPAA 
research requirements.  

If derived from a medical record, identify source:
UCSF medical record or other patient medical record
15.10  
Check all identifiers that will be collected and included in the research records, 
IDENTIFIERS: 
* 
even temporarily: (REQUIRED)
Names
Dates
Postal addresses (if only requesting/receiving zip codes check Yes to the Zip Code question 
below instead of checking this box)
Phone numbers
Fax numbers
Email addresses
Social Security Numbers*
Medical record numbers
Health plan numbers
Account numbers
License or certificate numbers
Vehicle ID numbers
Device identifiers or serial numbers
Web URLs
IP address numbers
Biometric identifiers
Facial photos or other identifiable images
Any other unique identifier
None
Could study records include 
 photos or images (even 'unidentifiable' 
* 
ANY
ones): (REQUIRED)
 Yes  
 No
15.11  
 
: Some research data sets include zip codes. Will you be receiving data with zip codes 
* ZIP CODES
as the only portion of an address: (REQUIRED)
Checking 'Yes' here means that you will not be requesting access to any 
other data element of a patient's address. If you are requesting other parts 
of an address such as street names and address numbers, check 'No' here 
and check the box for 'Postal addresses' in the list of 18 PHI Identifiers in 
the previous question.
  Yes  
  No
15.12  
 
Will health information or other clinical data be accessed from UCSF Health, 
* PATIENT RECORDS: 
Benioff Children's Hospital Oakland, or Zuckerberg San Francisco General (ZSFG): (REQUIRED)
 Yes  
 No
15.13  
 
Provide a general description of the types of clinical 
* CLINICAL DATA - GENERAL DESCRIPTION: 
 
data that you are requesting access to: (REQUIRED)
We have requested access to patients' medical entire medical records because data regarding the 
patient's medical history and phenotype is required by the laboratory in order to inform the 

analysis of exome data, allows us to learn about the natural history and phenotypes of very rare 
conditions as part of this research study, and is also needed to assess the clinical utility of exome 
sequencing, which is a major focus of this study.
15.14  
: Will the medical record data include any 
* CHART/CLINIC NOTES AND OTHER FREE TEXT FIELDS
information extracted from free text fields: (REQUIRED)
 Yes  
 No
Data sets that include free text from fields such as chart notes, 
clinic notes, and other text fields are considered identifiable, even 
without direct identifiers. 
15.15  
Does the research require access to any of 
HIPAA - PERMISSION TO ACCESS SENSITIVE DATA: 
* 
the following types of health information from the medical record: (check all that apply) 
(REQUIRED)
Drug or alcohol abuse, diagnosis or treatment
HIV/AIDS testing information
Genetic testing information
Mental health diagnosis or treatment
None of the above
Important note: Ensure that participants initial the corresponding 
line(s) in Section C of the HIPAA authorization form during the 
consent process.
15.16  
 
 Are you requesting access to any 
* ACCESS TO OTHER SENSITIVE OR PROTECTED DATA:
sensitive health data not protected under HIPAA (any other health history that patients would 
expect to be kept private such as records relating to treatment for obesity, STDs, compulsive 
behaviors, embarrassing health conditions, sexual orientation and practices, etc.): (REQUIRED)
 Yes  
 No
* List the types of sensitive data and provide a scientific justification to 
support the request. The IRB may require additional safeguards to protect 
: 
the confidentiality of participants
(REQUIRED)
Some types of sensitive infomation may be utilized to help identify a diagnosis through exome 
sequencing. For example, we summarize the patient's phenotype for the laboratory so that it can 
inform their analysis of the exome data and so if they identify a genetic variant that may be 
diagnostic, they will be able to ascertain whether the associated phenotype fits with our patient's 
phenotype and the expected inheritence pattern. Such sensitive information could include 
descriptions of psychiatric symptoms that may be suggestive of a specific genetic condition, or 
consanguinity (which suggests that the lab should be looking for variants in genes associated with 
autosomal recessive conditions).
15.18  
 
* IDENTIFIABILITY OF FINAL DATA SET: (REQUIRED)
Which type of data set are you requesting IRB approval for:
A 
 does not include ANY of the 18 HIPAA 
de-identified data set
identifiers in the list above or any free text fields.
A 
 (LDS) is described as health information that 
limited data set
excludes direct identifiers but that may include:
City
State

ZIP Code
Elements of date (including dates such as admission, discharge, 
service, month and year)
Other numbers, characteristics, or codes not listed as direct 
identifiers, including ages in years, months or days or hours
 include direct identifiers and/or information from 
Identifiable data sets
free text fields.
Review the 
 for more details about 
HIPAA FAQs on the IRB website
identifiability of data sets.
De-identified data set 
Limited data set 
Identifiable data set without direct identifiers (includes free text fields) 
Identifiable data set with direct identifiers (may or may not also include free text fields) 
15.19  
(check all that apply): 
* DATA COLLECTION AND STORAGE: 
(REQUIRED)
Collection methods:
Electronic case report form systems (eCRFs), such as OnCore or sponsor-provided clinical trial 
management portal
UCSF ITS approved Web-based online survey tools: Qualtrics or RedCap
Other web-based online surveys or computer-assisted interview tool
Mobile applications (mobile or tablet-based)
Text Messaging
Wearable devices
Audio/video recordings
Photographs
Paper-based (surveys, logs, diaries, etc.)
Other:
What online survey or computer assisted interview tool will you use: 
* 
(REQUIRED)
Qualtrics (Recommended)
RedCAP (Recommended)
Survey Monkey (NOT recommended and may require UCSF ITS Security review)
Other
Data will be collected/stored in systems owned by (check all that apply): 
* 
(REQUIRED)
Study sponsor
UCSF data center (including OnCore, RedCap, Qualtrics, and MyResearch)
UCSF encrypted server, workstation, or laptop residing outside of UCSF data center
Personal devices, such as laptops or tablets that are not owned or managed by UCSF
SF VAMC
Zuckerberg San Francisco General Hospital
Benioff Children's Hospital Oakland
Langley Porter Psychiatric Institution
Other UCSF affiliate clinic or location (specify below)
Cloud vendor such as Amazon Web Services (AWS), Salesforce, etc. (specify below)
Other academic institution
3rd party vendor (business entity)
Other (explain below)

Provide more details about where study data will be stored: 
* 
(REQUIRED)
Secure UCSF Box folders, which are HIPAA compliant.
15.20  
 Will patient records reviewed under this approval be 
* ADDITION OF RECORDS TO A REGISTRY:
added to a research database, repository, or registry (either already existing or established under 
this protocol): (REQUIRED)
 Yes  
 No
This activity generally requires patient consent and HIPAA 
Authorization  A Waiver of Consent/Authorization may be granted 
.
for patients who are deceased or lost to follow up, but ongoing 
patients should be consented at their next clinic visit prior to 
accessing their health records or they may provide consent and 
HIPAA authorization for research use of their health information by 
mail or through a certified E-Signature system such as 
DocuSign. You may be asked to revise your consent plans.
15.21  
During the lifecycle of data collection, transmission, and storage, will identifiable 
DATA SHARING: 
* 
 
information be shared with or be accessible to anyone outside of UCSF: (REQUIRED)
  Yes  
  No
16.0
 Financial Considerations
16.1  
Will subjects be paid for participation, reimbursed for time or expenses, or receive any 
* PAYMENT: 
other kind of compensation: (REQUIRED)
 Yes  
 No
16.2  
Subjects payment or compensation method (check all that apply):
PAYMENT METHODS: 
Payments will be (check all that apply):
Cash
Check
Gift card
Debit card
UCSF Research Subject Payment Card
Reimbursement for parking and other expenses
Other:
16.3  
Describe the schedule and amounts of payments, including the total subjects 
PAYMENT SCHEDULE: 
can receive for completing the study:
If there are multiple visits over time, explain how payments will be prorated for partial 
completion
If deviating from recommendations in Subject Payment Guidelines, include specific 
justification below
Subjects who complete the return of results survey will receive a $20 gift card to Safeway or 
Target as a thank you gift for their time. Subjects who complete the survey for the 5-7 month 
follow-up visit will receive a $30 gift card to Safeway or Target. The gift cards are per family, so 

one parent will be asked to complete the surveys on behalf of the family. Most families will have 
the opportunity to complete surveys and receive the gift cards, however some families 
(approximately 70) who agreed to be interviewed by our ethics (ELSI) team will not be asked to 
do surveys and will receive gift cards as part of the separate ELSI study IRB protocol for 
participating in interviews.
16.4  
Will subjects or their insurance be charged for any study activities:
COSTS TO SUBJECTS: 
 Yes  
 No
Describe the costs that may be incurred by subjects or 3rd party payers as 
a result of participation:
Explain why it is appropriate to charge those costs to the subjects
ompare subjects’ costs to the charges 
If this is a therapeutic study, c
that would typically be associated with receiving care off-study (e.g. is 
it more expensive to participate in this study than to receive care off-
study?)
Insurance will be billed for patient visits, as the visits are part of standard care. Consent and 
follow-up will be conducted when patients are seen during routine clinical visits.
17.0
 Other Approvals and Registrations
17.1  
 
Does this study involve administration of vaccines 
* ADMINISTRATION OF RECOMBINANT DNA: 
produced using recombinant DNA technologies to human subjects 
: 
(Help Link added Aug '15)
(REQUIRED)
  Yes  
  No
17.2  
Does this study involve human gene therapy: 
* HUMAN GENE THERAPY: 
(REQUIRED)
  Yes  
  No
17.4  
Indicate if this study involves other regulated materials and requires approval 
OTHER APPROVALS: 
and/or authorization from the following regulatory committees:
Institutional Biological Safety Committee (IBC)
Specify BUA #:
Institutional Animal Care and Use Committee (IACUC)
Specify IACUC #:
Controlled Substances
18.0
 Qualifications of Key Study Personnel and Affiliated 
Personnel
 

NEW: January 2019 - Affiliated personnel who do not 
need access to iRIS no longer need to get a UCSF ID. 
Instead, add them below in the Affiliated Personnel 
table below. 
18.1  
 
Qualifications of Key Study Personnel:
Instructions:
 
For UCSF Key Study Personnel (KSP)* listed in 
 select the KSP 
Section 3.0,
from the drop down list and add a description of their study responsibilities, 
qualifications and training. In study responsibilities, identify every individual 
who will be involved in the consent process. Under qualifications, please 
include:
Academic Title
Institutional Affiliation (UCSF, SFGH, VAMC, etc.)
Department
Certifications
NOTE: This information is required and your application will be 
 
considered incomplete without it. If this study involves invasive or 
risky procedures, or procedures requiring special training or 
certification, please identify who will be conducting these 
procedures and provide details about their qualifications and 
training. Click the orange question mark for more information and 
examples. 
 
Training Requirements: 
The IRB requires that all Key Study Personnel complete Human Subjects 
Protection Training through 
 prior to approval of a new study, or a 
CITI
modification in which KSP are being added. More information on the CITI 
training requirement can be found on our 
. 
website  
 
* Definition of Key Study Personnel and CITI Training Requirements (Nov, 
 UCSF Key Study Personnel include the Principal Investigator, other investigators 
2015):
and research personnel who are directly involved in conducting research with study 
participants or who are directly involved in using study participants’ identifiable private 
information during the course of the research. Key Personnel also include faculty mentors
/advisors who provide direct oversight to Postdoctoral Fellows, Residents and Clinical 
Fellows serving as PI on the IRB application.
 
KSP Name
Description of Study 
Responsibilities - Briefly 
describe what will each 
person be doing on the study. 
If there are procedures 
requiring special expertise or 
certification, identify who will 
be carrying these out. Also 
identify who will be obtaining 
informed consent.
Qualifications, Licensure, and 
Training
Dr Anne Slavotinek is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 

Dr. Slavotinek, Anne PhD, 
PhD
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO, and 
from her colleagues who 
see patients in and 
outside UCSF. She will be 
responsible for the 
conduct of this study, for 
obtaining consent and for 
ensuring adequate data 
sharing if next-
generation studies are 
performed.
Dr Slavotinek has many 
years of experience in 
tissue banking protocols 
and molecular genetics 
research.
Dr. Gallagher, Renata MD, 
PhD , MD, PhD
Dr Renata Gallagher is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Tenney, Jessica L
Dr Jessica Tenney is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Dr. Shieh, Joseph, MD, 
PhD
Dr Joseph Shieh is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Gardner, Marisa A
Dr Marisa Gardner is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at BCHO.
Board-certified Pediatric 
Neurologist who has 
experience with consent 
for exome sequencing.
Dr. Sherr, Elliott MD, PhD
Dr Elliott Sherr is a 
Board-certified 
neurologist who has 
Attending privileges at 
UCSF. He will recruit 
patients for this study 
Board-certified Pediatric 
Neurologist who has 
experience with consent 
for exome sequencing.

from those seen as 
inpatients or outpatients 
at UCSF.
Strober, Jonathan
Dr Jonathan Strober is a 
Board-certified 
neurologist who has 
Attending privileges at 
UCSF. He will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF.
Board-certified Pediatric 
Neurologist who has 
experience with consent 
for exome sequencing.
Dr. Weiss, William MD, PhD
Dr William Weiss is a 
Board-certified 
neurologist who has 
Attending privileges at 
UCSF. He will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at ZSFGH
Board-certified Pediatric 
Neurologist who has 
experience with consent 
for exome sequencing.
Dr. Koenig, Barbara, PhD
Dr Barbara Koenig is an 
anthropologist who is 
involved in 
ethnographical research 
at UCSF.
Anthropologist involved 
in ethnographical aspects 
of this research.
Anguiano, Beatriz
Study Coordinator
Ms. Anguiano is certified 
in human subjects 
research
Sahin Hodoglugil, Nuriye N
Program Manager
Dr. Nuriye Nalan Sahin 
Hodoglugil, MD, MA, 
DrPH is the Program 
Manager for the P3EGS 
Project. Previously she 
worked in global health, 
and collaborated with 
partners in academia, 
Ministries of Health and 
international health 
organizations to generate 
evidence to guide 
programs and policy for 
improving women's 
health. She worked in 
reproductive health 
programs and research in 
several countries in sub-
saharan Africa and Asia, 
as well as monitoring and 
evaluation of large scale 
maternal health 
interventions. She has 
also worked as a 
researher at UC San 
Francisco and UC 
Berkeley, and as a Senior 
Reproductive Health 
Technical Advisor at 
Johns Hopkins University. 

She holds an MD from 
Hacettepe University 
Faculty of Medicine, 
Turkey; an MA in cultural 
anthropology from 
Hacettepe University 
Institute of Social 
Sciences, and a DrPH 
from University of 
California, Berkeley.
Rego, Shannon M
Genetic Counselor. 
Responsibilities include 
recruiting and consenting 
subjects, returning 
results, entering data, 
and administering 
surveys.
Ms. Rego is a Licensed 
Clinical Genetic 
Counselor. She received 
her MS from Stanford 
University in 2014, and 
has worked with whole 
genome and whole 
exome sequencing since 
2014, joining our team in 
late 2017.
Hoban, Hannah G
Assistant Clinical 
Research Coordinator. 
Responsibilities include 
recruiting and consenting 
subjects, entering data, 
and administering 
surveys.
Ms. Hoban holds a BS in 
Human Physiology, is a 
licensed phlebotomist, 
and has research 
experience. She is CITI 
certified in human 
subjects research.
Outram, Simon M
Research Associate: Dr. 
Outram will conduct 
ethnographic 
observations and 
interviews.
Dr. Outram, PhD, MSC, 
MA, is certified in human 
subjects research. He has 
done research in Cultural 
Anthropology, Qualitative 
Social Research, Science 
and Technology Studies, 
and Bioethics. He has 
experience with multiple 
social science research 
methodologies, including 
in-depth interviewing and 
ethnographic observation.
Fairley, Cecilia F
Genetic Counselor. 
Responsibilities include 
recruiting and consenting 
subjects, entering data, 
and administering 
surveys.
Ms. Fairley is a Licensed 
Clinical Genetic 
Counselor who has 
worked with genetics 
outpatients at BCHO for 
the past several years.
Lianoglou, Billie R
Genetic Counselor. 
Responsibilities include 
recruiting and consenting 
subjects, returning 
results entering data, 
and administering 
surveys.
Ms. Lianoglou is a 
Licensed Clinical Genetic 
Counselor with ten years 
of experience.
Research Associate: Dr. 
Ackerman is leading the 
Dr. Ackerman, PhD, MPH 
is an assistant professor 
of social and behavioral 

Ackerman, Sara, PhD, MPH
ethnographic portion of 
the study and will be 
conducting observations 
and interviews.
sciences and has many 
years of experience in 
ethnography and 
qualitative genomic 
research.
Dr. Klein, Ophir MD
Dr. Ophir Klein is a Board-
certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. He will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Yip, Tiffany A
Genetic Counselor. 
Responsibilities include 
recruiting and consenting 
subjects, entering data, 
and administering 
surveys.
Ms. Yip is a licensed 
genetic counselor with 
experience consenting 
patients for exome 
sequencing.
Tam, Allison C
Dr. Allison Tam is a 
Board-certified Clinical 
Geneticist who has 
Attending privileges at 
UCSF. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at UCSF and BCHO.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Curry, Cynthia
Dr. Cynthia Curry is a 
Board-certified Clinical 
Geneticist at UCSF 
Fresno. She will recruit 
patients for this study 
from those seen as 
inpatients or outpatients 
at Community Regional 
Medical Center.
Board-certified Clinical 
Geneticist who has 
experience with consent 
for exome sequencing.
Patel, Sachi
Clinical Research 
Coordinator. 
Responsibilities include 
recruiting and consenting 
subjects, entering data, 
and administering 
surveys.
Ms. Patel holds a degree 
from UC Irvine in Public 
Health Sciences and has 
over a year of experience 
as a research coordinator.
Faubel, Amanda J
Clinical research 
coordinator: 
Responsibilities include 
recruiting and consenting 
subjects, entering data, 
and administering 
surveys.
Ms. Faubel holds a 
degree from Cal Poly in 
social sciences and has a 
year of experience as a 
research coordinator.
Dr. Gangaram is a 
medical geneticist and 

Gangaram, Balram
assistant professor who 
will assist with recruiting 
patients for this study at 
UCSF and UCSF Benioff 
Children's Hospital 
Oakland.
Medical geneticist with 
experience consenting for 
exome sequencing.
Chang, Jiyoo
Software developer
/research assistant: 
responsibilities include 
assisting with the 
development of the 
application being 
developed as part of this 
project (covered under a 
separate protocol) and 
assisting with utilizing 
the app to return results 
to families who have 
undergone exome 
sequencing
Ms. Chang holds a 
degree from Dartmouth 
and has over two years 
of experience with 
software development at 
UCSF.
Chin, Garrett
Data Manager
Mr. Chin holds a 
Bachelors of Science 
degree in Psychobiology 
(UC Davis), and Masters 
in Biological Sciences 
from Drexel University, 
College of Medicine. He is 
certified in human 
subjects research.
Prasad, Hannah L
Study coordinator. 
Responsibilities include 
administering surveys 
and entering data.
Ms. Prasad holds a 
Bachelors of Science 
degree in Biological 
Sciences (UC Davis) and 
Doctor of Medicine 
Degree from Universidad 
Autónoma de 
Guadalajara, Mexico. She 
is certified in human 
subjects research.
18.2  Affiliated Personnel:
Instructions:
 
This section is for personnel who are not listed in Section 3.0: Grant Key 
 because their names were not found in 
Personnel Access to the Study
the User Directory when 
 the iRIS Database and MyAccess directories 
both
were searched. Add any study personnel who fit 
 of the following criteria 
ALL
in the table below:
They meet the definition of Key Study Personnel (see above), and
They are associated with a UCSF-affiliated institution (e.g., VAMC, 
Gladstone, Institute on Aging, Vitalant, NCIRE, SFDPH, or ZSFG), and
They do 
 have a UCSF ID, 
not
and
They do 
 need access to the study application and other study 
not
materials in iRIS.

 in the 
Note: Attach a CITI Certificate for all persons listed below
Other 
 section of the 
Study Documents
Initial Review Submission Packet 
 after completing the 
.
Form
Study Application
 
Click the orange question mark icon to the right for more information on 
who to include and who not to include in this section.
 
Do 
 list personnel from outside sites/non-UCSF-affiliated institutions. 
not
Contacts for those sites (i.e. other institution, community-based site, 
foreign country, or Sovereign Native American nation) should be listed in 
the 
 section of the application.
Outside Sites
 
If there are no personnel on your study that meet the above 
criteria, leave this section blank.
 
Name
Institution
Telephone
E-mail
Role
No External Personnel has been added to this IRB Study
Please describe the study responsibilities and qualifications of each affiliated 
person listed above:
19.0
 End of Study Application
End of Study Application Form
 
:
To continue working on the Study Application
Click on the section you need to edit in the left-hand menu. Remember to save through 
the entire Study Application after making changes.
 
:
If you are done working on the Study Application
Before proceeding, please go back to Section 4.0 Initial Screening 
Important: 
Questions and 
 through the form to make sure all the relevant 
Save and Continue
sections and questions have been included. If you've changed any answers since you 
started, the branching may have changed. Your application will be incomplete and it will 
have to be returned for corrections. 
 
Once you are sure the form is complete, click 
. If this is a new 
Save and Continue
study, you will automatically enter the 
, 
Initial Review Submission Packet Form
where you can attach 
or other 
. Review the 
consent forms 
study documents
Initial 
 for a list of required attachments.
Review Submission Checklist
 
Answer all questions and attach all required documents to speed up your 
approval.
 
 
 
 
 
The UCSF IRB welcomes feedback about the IRB Study Application Form. Please click the link to 
answer a 
 about the application form.
survey