Datasets:

Fernandosr85
/

adaption-shoc2-ns-lah-variant-reports

prompt stringlengths 441 807	completion stringlengths 3.84k 5.6k	enhanced_prompt stringlengths 824 2.55k	enhanced_completion stringlengths 3.51k 7.94k
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu176Ser. Assigned investigation tier: Tier 1 — highest priority. Investigation score: 13/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evi...	Variant: SHOC2 p.Leu176Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 13/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.998...	Explain the assigned active-investigation tier for the SHOC2 missense variant p.Leu176Ser based on the data provided below. ### Critical Constraints - Preserve Values Exactly: You must state the Assigned Investigation Tier as "Tier 1 — highest priority" and the Investigation Score as "13/15" verbatim. - **No Recla...	Variant Identification and Gene Context Variant: SHOC2 p.Leu176Ser Assigned Tier: Tier 1 — highest priority Investigation Score: 13/15 SHOC2 encodes a leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) that functions within the SHOC2-MRAS-PP1c (SMP) ternary complex to facilitate depho...
Given this SHOC2 variant evidence profile — p.Ile513Thr, assigned tier Tier 2 — strong priority, investigation score 10/15, CADD PHRED 32.0 (cadd_phred_final), AlphaMissense score 0.900, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 18 (Repeat: LRR 18 — LRR scaffold domain, aa 101-563...	Variant: SHOC2 p.Ile513Thr (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.900 ...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. You must strictly adhere to the assigned tier (Tier 2) without suggesting a change. Variant Evidence Profile: - Variant: p.Ile513Thr - Assigned Tier: Tier 2 - Priority Level: Strong - **Investigation...	Variant Analysis: SHOC2 p.Ile513Thr ASSIGNED TIER: Tier 2 — strong priority Investigation score: 10/15 --- ### Evidence Summary The p.Ile513Thr variant in SHOC2 presents a compelling computational and structural profile for research prioritization. The variant is absent from gnomAD, consistent with ex...
Given this SHOC2 variant evidence profile — p.Asn527Ser, assigned tier Tier 3 — follow-up priority, investigation score 7/15, CADD PHRED 28.6 (cadd_phred_final), AlphaMissense score 0.962, AlphaMissense model class likely pathogenic, rare (gnomAD AF 8.55e-05), LRR repeat unit 19 (Repeat: LRR 19 — LRR scaffold domain, a...	Variant: SHOC2 p.Asn527Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 3 — follow-up priority Investigation score (source-derived, do not modify): 7/15 Evidence profile: - CADD PHRED: high (PHRED 28.6 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.962 (Al...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. Constraints: - Do not change the assigned tier (Tier 3). - Base your rationale strictly on the provided data points. Variant Evidence Profile: - Variant: p.Asn527Ser - Assigned Tier: Tier 3 - **Fol...	Variant Identification and Classification Status * Variant: p.Asn527Ser * Assigned Tier: Tier 3 — follow-up priority * Investigation Score: 7/15 Computational Evidence Summary The p.Asn527Ser variant demonstrates strong computational concordance indicative of potential functional impact. The ...
Explain the source-derived research-prioritization assessment for SHOC2 variant p.Asn248Thr in the context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). Assigned investigation tier: Tier 1 — highest priority. Investigation score: 11/15. Preserve these values exactly in your response. Do not reclassif...	Variant: SHOC2 p.Asn248Thr (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 11/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	# Task: Explain Source-Derived Research-Prioritization Assessment Provide a detailed explanation of the research-prioritization assessment for the SHOC2 variant p.Asn248Thr within the clinical context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). ## Critical Constraints - **Assigned Investi...	# Research-Prioritization Assessment: SHOC2 p.Asn248Thr ## Variant and Clinical Context Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein, 582 aa, UniProt Q9UQ13) Variant: p.Asn248Thr Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) SHOC2 encodes the only non-kinas...
Explain why SHOC2 p.Pro162Leu was assigned to Tier 1 — highest priority. Investigation score: 12/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=32.0 (cadd_phred_final), AlphaMissense score=0.995, AlphaMissense model class=li...	Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.995...	# Task: Explain Tier 1 Assignment for SHOC2 p.Pro162Leu Provide a detailed explanation of why the variant SHOC2 p.Pro162Leu was assigned to Tier 1 (highest priority) with an Investigation score of 12/15. ### Constraints - Mandatory Preservation: You must include the phrases "Tier 1" and "Investigation...	### Variant Interpretation Report: SHOC2 p.Pro162Leu Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, UniProt Q9UQ13) ASSIGNED TIER: Tier 1 Investigation score: 12/15 --- ### Evidence Summary The variant p.Pro162Leu has been assigned to Tier 1 based on convergent computational evidence, populat...
Provide a structured interpretation of SHOC2 p.Pro162Leu. The source pipeline assigned: Tier 1 — highest priority; investigation score: 12/15. Do not change these labels. Use CADD PHRED (cadd_phred_final: external API > VEP plugin), AlphaMissense score, AlphaMissense model class, gnomAD frequency, LRR domain context (R...	Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	Provide a structured interpretation of the SHOC2 variant p.Pro162Leu based on the following fixed source pipeline data, which must not be altered: - Priority Tier: Tier 1 (highest priority) - Investigation Score: 12/15 Your analysis must explicitly incorporate and evaluate the following specific criteria: 1....	# Variant Interpretation: SHOC2 p.Pro162Leu Variant: p.Pro162Leu Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein, UniProt Q9UQ13) Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) --- ## Evidence Summary ### CADD PHRED Score - Value: 32.0 (source: `cadd_p...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Thr515Ile. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 10/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evid...	Variant: SHOC2 p.Thr515Ile (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: high (PHRED 27.5 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.951 (Alph...	Explain the assigned active-investigation tier for the SHOC2 missense variant p.Thr515Ile based on the data provided below. ### Critical Constraints - Preserve Values Exactly: You must state the Assigned Investigation Tier as "Tier 2 — strong priority" and the Investigation Score as "10/15" verbatim. - **No Reclas...	### Variant Interpretation Summary: SHOC2 p.Thr515Ile Variant: SHOC2 missense variant p.Thr515Ile UniProt Accession: Q9UQ13 Assigned investigation tier: Tier 2 — strong priority Investigation score: 10/15 --- #### Computational and Predictor Evidence The p.Thr515Ile variant demonstrates maxi...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu493Phe. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 8/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evide...	Variant: SHOC2 p.Leu493Phe (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 8/15 Evidence profile: - CADD PHRED: high (PHRED 29.8 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.981 (Alpha...	# Task: Explain the Assigned Investigation Tier for SHOC2 Variant Analyze the provided data for the SHOC2 missense variant p.Leu493Phe and explain the rationale behind its assigned active-investigation tier. ## Critical Constraints 1. Preserve Values Exactly: You must include the following values verbatim...	# Variant Investigation Report: SHOC2 p.Leu493Phe ## Variant Identification * Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein) * Protein Change: p.Leu493Phe * UniProt Accession: Q9UQ13 (582 aa) * Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) ## Computationa...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu194Phe. Assigned investigation tier: Tier 1 — highest priority. Investigation score: 12/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evi...	Variant: SHOC2 p.Leu194Phe (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: very high (PHRED 31.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.998...	# Task: Explain the Active-Investigation Tier for SHOC2 Variant p.Leu194Phe Provide a detailed explanation for the assigned investigation tier of the SHOC2 missense variant p.Leu194Phe. ## Critical Constraints - Preserve Values Exactly: You must include the following values verbatim in your response: -...	# Variant Investigation Report: SHOC2 p.Leu194Phe ## Variant Identification - Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein) - Protein Change: p.Leu194Phe - Protein Context: SHOC2 (582 aa, UniProt Q9UQ13) is a leucine-rich repeat scaffold protein — the largest protein and the only non-kinase, non...
Given this SHOC2 variant evidence profile — p.Asn434Asp, assigned tier Tier 2 — strong priority, investigation score 10/15, CADD PHRED 35.0 (cadd_phred_final), AlphaMissense score 0.902, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 15 (Repeat: LRR 15 — LRR scaffold domain, aa 101-563...	Variant: SHOC2 p.Asn434Asp (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: very high (PHRED 35.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.902 ...	You are an expert geneticist and variant curator. Analyze the following SHOC2 variant evidence profile to explain the research-prioritization rationale. Constraint: You must justify the prioritization based on the provided data without challenging or changing the assigned tier (Tier 2). **Variant Evidence Profil...	Variant Identification * Gene: SHOC2 * Variant: p.Asn434Asp * Assigned Tier: Tier 2 — strong priority * Investigation Score: 10/15 Computational Evidence Synthesis The p.Asn434Asp variant demonstrates a high burden of computational evidence supporting potential functional impact. The CA...
Explain why SHOC2 p.Gln269Leu was assigned to Tier 1 — highest priority. Investigation score: 14/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=31.0 (cadd_phred_final), AlphaMissense score=0.991, AlphaMissense model class=li...	Variant: SHOC2 p.Gln269Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 14/15 Evidence profile: - CADD PHRED: very high (PHRED 31.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.991...	# Task: Justify SHOC2 Variant Tier Assignment Explain why the variant SHOC2 p.Gln269Leu was assigned to Tier 1 (highest priority) with an Investigation score of 14/15. ## Constraints - Mandatory Preservation: You must include the following labels verbatim in your response: "Tier 1" and "Investigation ...	Variant: SHOC2 p.Gln269Leu ASSIGNED TIER: Tier 1 Investigation score: 14/15 --- ### Evidence Synthesis and Scoring Rationale The assignment of Tier 1 to SHOC2 p.Gln269Leu reflects the maximum investigation score observed within the SHOC2 dataset, exceeding the established threshold (≥11) for highest...
Given this SHOC2 variant evidence profile — p.Pro300Ser, assigned tier Tier 2 — strong priority, investigation score 9/15, CADD PHRED 26.7 (cadd_phred_final), AlphaMissense score 0.989, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 9 (Repeat: LRR 9 — LRR scaffold domain, aa 101-563, U...	Variant: SHOC2 p.Pro300Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 26.7 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.989 (Alpha...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. You must strictly adhere to the assigned tier (Tier 2) without proposing any changes to it. Variant Evidence Profile: - Variant: p.Pro300Ser - Assigned Tier: Tier 2 - Priority: Strong - **Investigati...	Variant: SHOC2 p.Pro300Ser (LRR scaffold protein, UniProt Q9UQ13) ASSIGNED TIER: Tier 2 — strong priority Investigation Score: 9/15 --- ### Evidence Summary The p.Pro300Ser variant exhibits a robust computational profile characterized by maximum predictor concordance and high deleteriousness scores, c...
Explain why SHOC2 p.Gln269Arg was assigned to Tier 1 — highest priority. Investigation score: 12/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=28.9 (cadd_phred_final), AlphaMissense score=0.993, AlphaMissense model class=li...	Variant: SHOC2 p.Gln269Arg (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: high (PHRED 28.9 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.993 (Alp...	# Task: Justify SHOC2 Variant Tier Assignment Explain why the variant SHOC2 p.Gln269Arg was assigned to Tier 1 (highest priority) with an Investigation score: 12/15. ## Constraints - Verbatim Preservation: You must preserve the assigned tier and score labels exactly as provided: "Tier 1" and "Investi...	# Variant Prioritization Justification: SHOC2 p.Gln269Arg Variant: SHOC2 p.Gln269Arg ASSIGNED TIER: Tier 1 Investigation score: 12/15 --- ## Evidence Summary The assignment of p.Gln269Arg to Tier 1 is supported by convergent high-impact computational predictions, extreme population rarity, and c...
Explain the source-derived research-prioritization assessment for SHOC2 variant p.Asn527Ile in the context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). Assigned investigation tier: Tier 1 — highest priority. Investigation score: 11/15. Preserve these values exactly in your response. Do not reclassif...	Variant: SHOC2 p.Asn527Ile (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 11/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	# Task: Explain Source-Derived Research-Prioritization Assessment Provide a detailed explanation of the research-prioritization assessment for the SHOC2 variant p.Asn527Ile within the specific clinical context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). ## Critical Constraints - **Mandato...	# Research-Prioritization Assessment: SHOC2 p.Asn527Ile Variant: SHOC2 p.Asn527Ile (c.1580A>T) Protein: SHOC2 leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) Condition Context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) ## Assigned Pipeline Labels (Source-Derived — Pres...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Val188Met. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 9/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evide...	Variant: SHOC2 p.Val188Met (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 29.6 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.909 (Alpha...	### Task Explain the rationale for the assigned active-investigation tier for the SHOC2 missense variant p.Val188Met based on the provided evidence. ### Constraints - Preserve Values Exactly: You must include the following values verbatim in your response: - Assigned investigation tier: Tier 2 — strong priority ...	###Variant Interpretation Report: SHOC2 p.Val188Met Variant: p.Val188Met Protein: SHOC2 leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) Condition Context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) Assigned investigation tier: Tier 2 — strong priority **Investig...
Explain why SHOC2 p.Pro534Ala was assigned to Tier 2 — strong priority. Investigation score: 9/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=29.1 (cadd_phred_final), AlphaMissense score=0.997, AlphaMissense model class=like...	Variant: SHOC2 p.Pro534Ala (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 29.1 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.997 (Alpha...	# Task: Explain Variant Tier Assignment Explain why the variant SHOC2 p.Pro534Ala was assigned to Tier 2 — strong priority with an Investigation score: 9/15. ## Constraints - The assigned tier ("Tier 2 — strong priority") and score ("9/15") are source-derived pipeline labels. You must preserve these labe...	### Variant Tier Assignment Rationale: SHOC2 p.Pro534Ala Variant: SHOC2 p.Pro534Ala ASSIGNED TIER: Tier 2 — strong priority Investigation score: 9/15 --- #### Structural and Functional Context SHOC2 encodes a leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) — the largest and sole non-...

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This dataset is a remastered version prepared using Adaption's Adaptive Data platform.

adaption-shoc2_ns_lah_variant_reports

This dataset contains structured research-level assessments of SHOC2 missense variants associated with Noonan Syndrome with Loose Anagen Hair (NS-LAH). Each entry provides a detailed interpretation including computational scores (CADD, AlphaMissense), population frequency, LRR domain context, and SMP complex proximity. The reports preserve source-derived Tier 1 prioritization labels and investigation scores for functional follow-up without making clinical classifications.

Dataset size

There are 158 data points in this dataset. This is an instruction tuning dataset.

Quality of Remastered Dataset

The final quality is A, with a relative quality improvement of 21.2%.

Domain

Science (71%)
Medical (24%)
Other (5%)

Language

English (100%)

Tone

Technical (95%)
Analytical (5%)

Evaluation Results

Quality Gains:
Grade Improvement:
Percentile Chart:

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prompt stringlengths 441 807	completion stringlengths 3.84k 5.6k	enhanced_prompt stringlengths 824 2.55k	enhanced_completion stringlengths 3.51k 7.94k
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu176Ser. Assigned investigation tier: Tier 1 — highest priority. Investigation score: 13/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evi...	Variant: SHOC2 p.Leu176Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 13/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.998...	Explain the assigned active-investigation tier for the SHOC2 missense variant p.Leu176Ser based on the data provided below. ### Critical Constraints - Preserve Values Exactly: You must state the Assigned Investigation Tier as "Tier 1 — highest priority" and the Investigation Score as "13/15" verbatim. - **No Recla...	Variant Identification and Gene Context Variant: SHOC2 p.Leu176Ser Assigned Tier: Tier 1 — highest priority Investigation Score: 13/15 SHOC2 encodes a leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) that functions within the SHOC2-MRAS-PP1c (SMP) ternary complex to facilitate depho...
Given this SHOC2 variant evidence profile — p.Ile513Thr, assigned tier Tier 2 — strong priority, investigation score 10/15, CADD PHRED 32.0 (cadd_phred_final), AlphaMissense score 0.900, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 18 (Repeat: LRR 18 — LRR scaffold domain, aa 101-563...	Variant: SHOC2 p.Ile513Thr (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.900 ...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. You must strictly adhere to the assigned tier (Tier 2) without suggesting a change. Variant Evidence Profile: - Variant: p.Ile513Thr - Assigned Tier: Tier 2 - Priority Level: Strong - **Investigation...	Variant Analysis: SHOC2 p.Ile513Thr ASSIGNED TIER: Tier 2 — strong priority Investigation score: 10/15 --- ### Evidence Summary The p.Ile513Thr variant in SHOC2 presents a compelling computational and structural profile for research prioritization. The variant is absent from gnomAD, consistent with ex...
Given this SHOC2 variant evidence profile — p.Asn527Ser, assigned tier Tier 3 — follow-up priority, investigation score 7/15, CADD PHRED 28.6 (cadd_phred_final), AlphaMissense score 0.962, AlphaMissense model class likely pathogenic, rare (gnomAD AF 8.55e-05), LRR repeat unit 19 (Repeat: LRR 19 — LRR scaffold domain, a...	Variant: SHOC2 p.Asn527Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 3 — follow-up priority Investigation score (source-derived, do not modify): 7/15 Evidence profile: - CADD PHRED: high (PHRED 28.6 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.962 (Al...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. Constraints: - Do not change the assigned tier (Tier 3). - Base your rationale strictly on the provided data points. Variant Evidence Profile: - Variant: p.Asn527Ser - Assigned Tier: Tier 3 - **Fol...	Variant Identification and Classification Status * Variant: p.Asn527Ser * Assigned Tier: Tier 3 — follow-up priority * Investigation Score: 7/15 Computational Evidence Summary The p.Asn527Ser variant demonstrates strong computational concordance indicative of potential functional impact. The ...
Explain the source-derived research-prioritization assessment for SHOC2 variant p.Asn248Thr in the context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). Assigned investigation tier: Tier 1 — highest priority. Investigation score: 11/15. Preserve these values exactly in your response. Do not reclassif...	Variant: SHOC2 p.Asn248Thr (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 11/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	# Task: Explain Source-Derived Research-Prioritization Assessment Provide a detailed explanation of the research-prioritization assessment for the SHOC2 variant p.Asn248Thr within the clinical context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). ## Critical Constraints - **Assigned Investi...	# Research-Prioritization Assessment: SHOC2 p.Asn248Thr ## Variant and Clinical Context Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein, 582 aa, UniProt Q9UQ13) Variant: p.Asn248Thr Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) SHOC2 encodes the only non-kinas...
Explain why SHOC2 p.Pro162Leu was assigned to Tier 1 — highest priority. Investigation score: 12/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=32.0 (cadd_phred_final), AlphaMissense score=0.995, AlphaMissense model class=li...	Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: very high (PHRED 32.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.995...	# Task: Explain Tier 1 Assignment for SHOC2 p.Pro162Leu Provide a detailed explanation of why the variant SHOC2 p.Pro162Leu was assigned to Tier 1 (highest priority) with an Investigation score of 12/15. ### Constraints - Mandatory Preservation: You must include the phrases "Tier 1" and "Investigation...	### Variant Interpretation Report: SHOC2 p.Pro162Leu Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, UniProt Q9UQ13) ASSIGNED TIER: Tier 1 Investigation score: 12/15 --- ### Evidence Summary The variant p.Pro162Leu has been assigned to Tier 1 based on convergent computational evidence, populat...
Provide a structured interpretation of SHOC2 p.Pro162Leu. The source pipeline assigned: Tier 1 — highest priority; investigation score: 12/15. Do not change these labels. Use CADD PHRED (cadd_phred_final: external API > VEP plugin), AlphaMissense score, AlphaMissense model class, gnomAD frequency, LRR domain context (R...	Variant: SHOC2 p.Pro162Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	Provide a structured interpretation of the SHOC2 variant p.Pro162Leu based on the following fixed source pipeline data, which must not be altered: - Priority Tier: Tier 1 (highest priority) - Investigation Score: 12/15 Your analysis must explicitly incorporate and evaluate the following specific criteria: 1....	# Variant Interpretation: SHOC2 p.Pro162Leu Variant: p.Pro162Leu Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein, UniProt Q9UQ13) Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) --- ## Evidence Summary ### CADD PHRED Score - Value: 32.0 (source: `cadd_p...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Thr515Ile. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 10/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evid...	Variant: SHOC2 p.Thr515Ile (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: high (PHRED 27.5 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.951 (Alph...	Explain the assigned active-investigation tier for the SHOC2 missense variant p.Thr515Ile based on the data provided below. ### Critical Constraints - Preserve Values Exactly: You must state the Assigned Investigation Tier as "Tier 2 — strong priority" and the Investigation Score as "10/15" verbatim. - **No Reclas...	### Variant Interpretation Summary: SHOC2 p.Thr515Ile Variant: SHOC2 missense variant p.Thr515Ile UniProt Accession: Q9UQ13 Assigned investigation tier: Tier 2 — strong priority Investigation score: 10/15 --- #### Computational and Predictor Evidence The p.Thr515Ile variant demonstrates maxi...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu493Phe. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 8/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evide...	Variant: SHOC2 p.Leu493Phe (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 8/15 Evidence profile: - CADD PHRED: high (PHRED 29.8 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.981 (Alpha...	# Task: Explain the Assigned Investigation Tier for SHOC2 Variant Analyze the provided data for the SHOC2 missense variant p.Leu493Phe and explain the rationale behind its assigned active-investigation tier. ## Critical Constraints 1. Preserve Values Exactly: You must include the following values verbatim...	# Variant Investigation Report: SHOC2 p.Leu493Phe ## Variant Identification * Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein) * Protein Change: p.Leu493Phe * UniProt Accession: Q9UQ13 (582 aa) * Associated Condition: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) ## Computationa...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Leu194Phe. Assigned investigation tier: Tier 1 — highest priority. Investigation score: 12/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evi...	Variant: SHOC2 p.Leu194Phe (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: very high (PHRED 31.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.998...	# Task: Explain the Active-Investigation Tier for SHOC2 Variant p.Leu194Phe Provide a detailed explanation for the assigned investigation tier of the SHOC2 missense variant p.Leu194Phe. ## Critical Constraints - Preserve Values Exactly: You must include the following values verbatim in your response: -...	# Variant Investigation Report: SHOC2 p.Leu194Phe ## Variant Identification - Gene: SHOC2 (SHOC2 leucine-rich repeat scaffold protein) - Protein Change: p.Leu194Phe - Protein Context: SHOC2 (582 aa, UniProt Q9UQ13) is a leucine-rich repeat scaffold protein — the largest protein and the only non-kinase, non...
Given this SHOC2 variant evidence profile — p.Asn434Asp, assigned tier Tier 2 — strong priority, investigation score 10/15, CADD PHRED 35.0 (cadd_phred_final), AlphaMissense score 0.902, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 15 (Repeat: LRR 15 — LRR scaffold domain, aa 101-563...	Variant: SHOC2 p.Asn434Asp (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 10/15 Evidence profile: - CADD PHRED: very high (PHRED 35.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.902 ...	You are an expert geneticist and variant curator. Analyze the following SHOC2 variant evidence profile to explain the research-prioritization rationale. Constraint: You must justify the prioritization based on the provided data without challenging or changing the assigned tier (Tier 2). **Variant Evidence Profil...	Variant Identification * Gene: SHOC2 * Variant: p.Asn434Asp * Assigned Tier: Tier 2 — strong priority * Investigation Score: 10/15 Computational Evidence Synthesis The p.Asn434Asp variant demonstrates a high burden of computational evidence supporting potential functional impact. The CA...
Explain why SHOC2 p.Gln269Leu was assigned to Tier 1 — highest priority. Investigation score: 14/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=31.0 (cadd_phred_final), AlphaMissense score=0.991, AlphaMissense model class=li...	Variant: SHOC2 p.Gln269Leu (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 14/15 Evidence profile: - CADD PHRED: very high (PHRED 31.0 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.991...	# Task: Justify SHOC2 Variant Tier Assignment Explain why the variant SHOC2 p.Gln269Leu was assigned to Tier 1 (highest priority) with an Investigation score of 14/15. ## Constraints - Mandatory Preservation: You must include the following labels verbatim in your response: "Tier 1" and "Investigation ...	Variant: SHOC2 p.Gln269Leu ASSIGNED TIER: Tier 1 Investigation score: 14/15 --- ### Evidence Synthesis and Scoring Rationale The assignment of Tier 1 to SHOC2 p.Gln269Leu reflects the maximum investigation score observed within the SHOC2 dataset, exceeding the established threshold (≥11) for highest...
Given this SHOC2 variant evidence profile — p.Pro300Ser, assigned tier Tier 2 — strong priority, investigation score 9/15, CADD PHRED 26.7 (cadd_phred_final), AlphaMissense score 0.989, AlphaMissense model class likely pathogenic, absent from gnomAD, LRR repeat unit 9 (Repeat: LRR 9 — LRR scaffold domain, aa 101-563, U...	Variant: SHOC2 p.Pro300Ser (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 26.7 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.989 (Alpha...	Analyze the following SHOC2 variant evidence profile and explain the research-prioritization rationale. You must strictly adhere to the assigned tier (Tier 2) without proposing any changes to it. Variant Evidence Profile: - Variant: p.Pro300Ser - Assigned Tier: Tier 2 - Priority: Strong - **Investigati...	Variant: SHOC2 p.Pro300Ser (LRR scaffold protein, UniProt Q9UQ13) ASSIGNED TIER: Tier 2 — strong priority Investigation Score: 9/15 --- ### Evidence Summary The p.Pro300Ser variant exhibits a robust computational profile characterized by maximum predictor concordance and high deleteriousness scores, c...
Explain why SHOC2 p.Gln269Arg was assigned to Tier 1 — highest priority. Investigation score: 12/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=28.9 (cadd_phred_final), AlphaMissense score=0.993, AlphaMissense model class=li...	Variant: SHOC2 p.Gln269Arg (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 12/15 Evidence profile: - CADD PHRED: high (PHRED 28.9 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.993 (Alp...	# Task: Justify SHOC2 Variant Tier Assignment Explain why the variant SHOC2 p.Gln269Arg was assigned to Tier 1 (highest priority) with an Investigation score: 12/15. ## Constraints - Verbatim Preservation: You must preserve the assigned tier and score labels exactly as provided: "Tier 1" and "Investi...	# Variant Prioritization Justification: SHOC2 p.Gln269Arg Variant: SHOC2 p.Gln269Arg ASSIGNED TIER: Tier 1 Investigation score: 12/15 --- ## Evidence Summary The assignment of p.Gln269Arg to Tier 1 is supported by convergent high-impact computational predictions, extreme population rarity, and c...
Explain the source-derived research-prioritization assessment for SHOC2 variant p.Asn527Ile in the context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). Assigned investigation tier: Tier 1 — highest priority. Investigation score: 11/15. Preserve these values exactly in your response. Do not reclassif...	Variant: SHOC2 p.Asn527Ile (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 1 — highest priority Investigation score (source-derived, do not modify): 11/15 Condition context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) research. SHOC2 encodes a leucine-rich r...	# Task: Explain Source-Derived Research-Prioritization Assessment Provide a detailed explanation of the research-prioritization assessment for the SHOC2 variant p.Asn527Ile within the specific clinical context of Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721). ## Critical Constraints - **Mandato...	# Research-Prioritization Assessment: SHOC2 p.Asn527Ile Variant: SHOC2 p.Asn527Ile (c.1580A>T) Protein: SHOC2 leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) Condition Context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) ## Assigned Pipeline Labels (Source-Derived — Pres...
Explain the assigned active-investigation tier for SHOC2 missense variant p.Val188Met. Assigned investigation tier: Tier 2 — strong priority. Investigation score: 9/15. Preserve these values exactly in your response. Do not reclassify, upgrade, downgrade, or replace the tier with generic High/Moderate/Low labels. Evide...	Variant: SHOC2 p.Val188Met (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 29.6 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.909 (Alpha...	### Task Explain the rationale for the assigned active-investigation tier for the SHOC2 missense variant p.Val188Met based on the provided evidence. ### Constraints - Preserve Values Exactly: You must include the following values verbatim in your response: - Assigned investigation tier: Tier 2 — strong priority ...	###Variant Interpretation Report: SHOC2 p.Val188Met Variant: p.Val188Met Protein: SHOC2 leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) Condition Context: Noonan Syndrome with Loose Anagen Hair (NS-LAH, OMIM 607721) Assigned investigation tier: Tier 2 — strong priority **Investig...
Explain why SHOC2 p.Pro534Ala was assigned to Tier 2 — strong priority. Investigation score: 9/15. The assigned tier and score are source-derived pipeline labels and must be preserved verbatim. Use the following evidence only: CADD PHRED=29.1 (cadd_phred_final), AlphaMissense score=0.997, AlphaMissense model class=like...	Variant: SHOC2 p.Pro534Ala (LRR scaffold protein, Q9UQ13) ASSIGNED TIER (source-derived, do not modify): Tier 2 — strong priority Investigation score (source-derived, do not modify): 9/15 Evidence profile: - CADD PHRED: high (PHRED 29.1 (cadd_phred_final: API > VEP plugin)) - AlphaMissense score: 0.997 (Alpha...	# Task: Explain Variant Tier Assignment Explain why the variant SHOC2 p.Pro534Ala was assigned to Tier 2 — strong priority with an Investigation score: 9/15. ## Constraints - The assigned tier ("Tier 2 — strong priority") and score ("9/15") are source-derived pipeline labels. You must preserve these labe...	### Variant Tier Assignment Rationale: SHOC2 p.Pro534Ala Variant: SHOC2 p.Pro534Ala ASSIGNED TIER: Tier 2 — strong priority Investigation score: 9/15 --- #### Structural and Functional Context SHOC2 encodes a leucine-rich repeat scaffold protein (582 aa, UniProt Q9UQ13) — the largest and sole non-...