Datasets:

Fernandosr85
/

adaption-rasopathy-vus-tier1-reports

instruction stringlengths 353 426	output stringlengths 1.03k 1.36k	enhanced_prompt stringlengths 730 2.79k	enhanced_completion stringlengths 1.99k 6.44k	accession stringlengths 12 12	cadd_phred float64 23.4 36	clingen_validity stringclasses 1 value	clinvar_id int64 12.6k 4.85M	condition_match_type stringclasses 2 values	gene stringclasses 10 values	investigation_score int64 8 14	investigation_tier stringclasses 1 value	n_concordant int64 2 5	omim_primary stringclasses 10 values	original_context stringlengths 186 261	primary_condition stringclasses 5 values	protein_change stringlengths 9 29	record_id stringlengths 12 12	reference_doi stringclasses 1 value	reference_pmid stringclasses 1 value	snapshot_date timestamp[s]date 2026-06-28 00:00:00 2026-06-28 00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: MAP2K1 Protein variant: ENSP00000302486.5:p.Cys142Arg ClinVar ID: 3338730 Investigation score: 13 CADD PHRED: 33.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context and state...	The ENSP00000302486.5:p.Cys142Arg variant (ClinVar ID: 3338730) in MAP2K1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 13, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Addition...	# Task: VUS Reclassification Analysis Analyze the provided Variant of Uncertain Significance (VUS) data to summarize the computational evidence level and gene–disease validity. Specifically: 1. Evidence Summary: Detail the computational evidence and gene–disease validity context using ClinGen and GenCC standards....	# Variant Prioritization and Evidence Analysis Report Date of Analysis: June 30, 2026 Variant Identification: MAP2K1 ENSP00000302486.5:p.Cys142Arg ClinVar Accession: 3338730 (VCV003338730) Associated Condition: Cardiofaciocutaneous syndrome (OMIM: 615279) Prioritization Tier: Tier 1 (Highes...	VCV003338730	33	Definitive	3,338,730	broader_clingen_entity	MAP2K1	13	Tier 1 — highest priority	4	615279	MAP2K1 3338730 VCV003338730 ENSP00000302486.5:p.Cys142Arg 13 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615279 40496714 10.1016/j.gimo.2025.103430 2026-06-28 2cf0855ca9d6	cardiofaciocutaneous syndrome	ENSP00000302486.5:p.Cys142Arg	2cf0855ca9d6	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: RIT1 Protein variant: ENSP00000357306.3:p.Asn134Ile ClinVar ID: 3633616 Investigation score: 11 CADD PHRED: 30.0 Concordant predictors: 5 Include the ClinGen and GenCC validity context and state w...	The ENSP00000357306.3:p.Asn134Ile variant (ClinVar ID: 3633616) in RIT1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 30.0, and support from 5 concordant computational predictor(s). Additional...	# Task: Clinical Variant Evidence Summary Analyze the provided Variant of Uncertain Significance (VUS) data to summarize the computational evidence level and gene–disease validity. Specifically, incorporate context from ClinGen (Clinical Genome Resource) and GenCC (Gene Curation Coalition) regarding validity. Conclude...	# Clinical Variant Evidence Summary ### 1. Computational Evidence Level The variant RIT1 p.Asn134Ile (ClinVar 3633616) is categorized as Tier 1 — highest priority for investigation. The computational metrics provided are: * Investigation Score: 11 * CADD PHRED Score: 30.0 * **Concordant Predictor Cou...	VCV003633616	30	Definitive	3,633,616	broader_clingen_entity	RIT1	11	Tier 1 — highest priority	5	615355	RIT1 3633616 VCV003633616 ENSP00000357306.3:p.Asn134Ile 11 Tier 1 — highest priority 30.0 5 Noonan syndrome Definitive broader_clingen_entity 615355 40496714 10.1016/j.gimo.2025.103430 2026-06-28 6fbe32f69775	Noonan syndrome	ENSP00000357306.3:p.Asn134Ile	6fbe32f69775	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: PTPN11 Protein variant: ENSP00000340944.3:p.Gly503Arg ClinVar ID: 40559 Investigation score: 14 CADD PHRED: 33.0 Concordant predictors: 4 Contextualize the gene–disease relationship ac...	The ENSP00000340944.3:p.Gly503Arg variant (ClinVar ID: 40559) in PTPN11 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 14, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additional...	# Task: Computational Prioritization Analysis for Genetic Variant Analyze the provided computational prioritization data for the selected candidate variant intended for additional functional investigation. Specifically: 1. Data Review: Examine the variant's investigation score, CADD PHRED score, and concordant pr...	# Computational Prioritization Analysis: PTPN11 p.Gly503Arg ## Variant Identification * Gene: PTPN11 * Protein Variant: ENSP00000340944.3:p.Gly503Arg * ClinVar ID: 40559 (VCV000040559) ## Computational Evidence Review The candidate variant exhibits the following computational metrics, representing in sili...	VCV000040559	33	Definitive	40,559	exact	PTPN11	14	Tier 1 — highest priority	4	176876	PTPN11 40559 VCV000040559 ENSP00000340944.3:p.Gly503Arg 14 Tier 1 — highest priority 33.0 4 Noonan syndrome with multiple lentigines Definitive exact 176876 40496714 10.1016/j.gimo.2025.103430 2026-06-28 0763cb6b21c6	Noonan syndrome with multiple lentigines	ENSP00000340944.3:p.Gly503Arg	0763cb6b21c6	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: RIT1 Protein variant: ENSP00000357306.3:p.Ala77Thr ClinVar ID: 183403 Investigation score: 11 CADD PHRED: 28.9 Concordant predictors: 4 Contextualize the gene–disease relationship acco...	The ENSP00000357306.3:p.Ala77Thr variant (ClinVar ID: 183403) in RIT1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 28.9, and support from 4 concordant computational predictor(s). Additional p...	# Task: Computational Prioritization Analysis for Gene Variant Analyze the provided computational prioritization data for the selected candidate variant intended for additional functional investigation. ## Instructions 1. Data Analysis: Review the variant metrics including the investigation score, CADD PHRED sco...	# Computational Prioritization Analysis: RIT1 Variant ## Variant Identification * Gene: RIT1 * Protein Variant: ENSP00000357306.3:p.Ala77Thr * ClinVar ID: 183403 * Associated Condition: Noonan syndrome (OMIM: 615355) ## Computational Evidence Metrics The following computational values are reported exa...	VCV000183403	28.9	Definitive	183,403	broader_clingen_entity	RIT1	11	Tier 1 — highest priority	4	615355	RIT1 183403 VCV000183403 ENSP00000357306.3:p.Ala77Thr 11 Tier 1 — highest priority 28.9 4 Noonan syndrome Definitive broader_clingen_entity 615355 40496714 10.1016/j.gimo.2025.103430 2026-06-28 65c731a51da7	Noonan syndrome	ENSP00000357306.3:p.Ala77Thr	65c731a51da7	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: BRAF Protein variant: ENSP00000493543.1:p.Glu501Lys ClinVar ID: 13977 Investigation score: 11 CADD PHRED: 32.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context an...	The ENSP00000493543.1:p.Glu501Lys variant (ClinVar ID: 13977) in BRAF was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Additional p...	# Task: Tier 1 Prioritization Analysis for Variant of Uncertain Significance (VUS) Based on the computational criteria and raw data provided below, describe the Tier 1 prioritization of this Variant of Uncertain Significance (VUS). Requirements: 1. Analysis: Evaluate the variant using the provided metrics (I...	# Tier 1 Prioritization Analysis: BRAF p.Glu501Lys ## Variant Identification * Gene: BRAF * Protein Variant: ENSP00000493543.1:p.Glu501Lys * ClinVar ID: 13977 * Associated Condition: Cardiofaciocutaneous syndrome (OMIM: 115150) ## Computational Evidence The prioritization of this variant is based on t...	VCV000013977	32	Definitive	13,977	broader_clingen_entity	BRAF	11	Tier 1 — highest priority	4	115150	BRAF 13977 VCV000013977 ENSP00000493543.1:p.Glu501Lys 11 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 115150 40496714 10.1016/j.gimo.2025.103430 2026-06-28 cec7afdae4e6	cardiofaciocutaneous syndrome	ENSP00000493543.1:p.Glu501Lys	cec7afdae4e6	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: MAP2K2 Protein variant: ENSP00000262948.4:p.Gly135Val ClinVar ID: 3061850 Investigation score: 12 CADD PHRED: 32.0 Concordant predictors: 4 Contextualize the gene–disease relationship ...	The ENSP00000262948.4:p.Gly135Val variant (ClinVar ID: 3061850) in MAP2K2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Addition...	Analyze the provided computational prioritization data for the selected gene variant candidate. Specifically: 1. Data Review: Examine the variant's metrics, including the Investigation score, CADD PHRED score, and number of concordant predictors. 2. Contextual Analysis: Contextualize the gene–disease relations...	### Variant Prioritization Analysis: MAP2K2 ENSP00000262948.4:p.Gly135Val #### 1. Computational Evidence Review The variant MAP2K2 ENSP00000262948.4:p.Gly135Val (ClinVar ID: 3061850) exhibits the following computational metrics: * Investigation Score: 12 * CADD PHRED Score: 32.0 * **Concordant Predictors...	VCV003061850	32	Definitive	3,061,850	broader_clingen_entity	MAP2K2	12	Tier 1 — highest priority	4	615280	MAP2K2 3061850 VCV003061850 ENSP00000262948.4:p.Gly135Val 12 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615280 40496714 10.1016/j.gimo.2025.103430 2026-06-28 7d6db66db411	cardiofaciocutaneous syndrome	ENSP00000262948.4:p.Gly135Val	7d6db66db411	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: MAP2K2 Protein variant: ENSP00000262948.4:p.Pro266Arg ClinVar ID: 3636796 Investigation score: 11 CADD PHRED: 33.0 Concordant predictors: 4 Clearly explain that Tier 1 represents a computational p...	The ENSP00000262948.4:p.Pro266Arg variant (ClinVar ID: 3636796) in MAP2K2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Addition...	# Task: Analyze Computational Evidence and Gene-Disease Validity Please summarize the computational evidence level and gene–disease validity associated with the provided Variant of Uncertain Significance (VUS) classified as Tier 1. Important Clarification: Clearly explain that "Tier 1" represents a computational...	### Computational Evidence Summary for MAP2K2 Variant (ClinVar ID: 3636796) Variant Identification * Gene: MAP2K2 * Protein Change: p.Pro266Arg (ENSP00000262948.4) * ClinVar Accession: VCV003636796 * Current Classification: Variant of Uncertain Significance (VUS) *Computational Metrics...	VCV003636796	33	Definitive	3,636,796	broader_clingen_entity	MAP2K2	11	Tier 1 — highest priority	4	615280	MAP2K2 3636796 VCV003636796 ENSP00000262948.4:p.Pro266Arg 11 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615280 40496714 10.1016/j.gimo.2025.103430 2026-06-28 33e7b63ddde0	cardiofaciocutaneous syndrome	ENSP00000262948.4:p.Pro266Arg	33e7b63ddde0	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: BRAF Protein variant: ENSP00000493543.1:p.Leu525Gln ClinVar ID: 520890 Investigation score: 11 CADD PHRED: 32.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context a...	The ENSP00000493543.1:p.Leu525Gln variant (ClinVar ID: 520890) in BRAF was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Additional ...	# Task: Tier 1 Prioritization Analysis for Variant of Uncertain Significance (VUS) Based on the computational criteria and raw data provided below, perform the following: 1. Describe the Tier 1 Prioritization: Analyze the variant's priority status using the provided metrics. 2. Contextualize Validity: Incorpo...	# Tier 1 Prioritization Analysis: BRAF p.Leu525Gln (ClinVar 520890) ## 1. Tier 1 Prioritization Description The variant BRAF ENSP00000493543.1:p.Leu525Gln (ClinVar ID: 520890) has been assigned a Tier 1 — highest priority status for computational investigation. This prioritization reflects a convergence of high-sc...	VCV000520890	32	Definitive	520,890	broader_clingen_entity	BRAF	11	Tier 1 — highest priority	4	115150	BRAF 520890 VCV000520890 ENSP00000493543.1:p.Leu525Gln 11 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 115150 40496714 10.1016/j.gimo.2025.103430 2026-06-28 25b4759eab5a	cardiofaciocutaneous syndrome	ENSP00000493543.1:p.Leu525Gln	25b4759eab5a	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: BRAF Protein variant: ENSP00000493543.1:p.Gly466Arg ClinVar ID: 44801 Investigation score: 12 CADD PHRED: 32.0 Concordant predictors: 4 Clarify which additional evidence, including func...	The ENSP00000493543.1:p.Gly466Arg variant (ClinVar ID: 44801) in BRAF was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Additional p...	# Task: VUS Tier 1 Prioritization and Reclassification Analysis Based on the computational criteria and raw data provided below, perform the following actions: 1. Describe the Tier 1 Prioritization: Analyze the Variant of Uncertain Significance (VUS) using the provided metrics (Investigation score, CADD PHRED, co...	# VUS Tier 1 Prioritization and Reclassification Analysis ## Variant Identification * Gene: BRAF * Protein Variant: ENSP00000493543.1:p.Gly466Arg * ClinVar ID: 44801 (VCV000044801) * Associated Condition: Cardiofaciocutaneous syndrome (OMIM: 115150) ## 1. Tier 1 Prioritization Analysis The var...	VCV000044801	32	Definitive	44,801	broader_clingen_entity	BRAF	12	Tier 1 — highest priority	4	115150	BRAF 44801 VCV000044801 ENSP00000493543.1:p.Gly466Arg 12 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 115150 40496714 10.1016/j.gimo.2025.103430 2026-06-28 68f743327f3a	cardiofaciocutaneous syndrome	ENSP00000493543.1:p.Gly466Arg	68f743327f3a	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Assess the clinical investigation priority of the following variant identified by the unified RASopathy VUS Series pipeline: Gene: MAP2K2 Protein variant: ENSP00000262948.4:p.Leu184Pro ClinVar ID: 2086788 Investigation score: 11 CADD PHRED: 32.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context ...	The ENSP00000262948.4:p.Leu184Pro variant (ClinVar ID: 2086788) in MAP2K2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Addition...	# Clinical Investigation Priority Assessment Assess the clinical investigation priority for the following variant identified by the unified RASopathy VUS (Variant of Uncertain Significance) Series pipeline. Required Analysis: 1. Evaluate the provided variant data. 2. Integrate ClinGen (Clinical Genome Resource) ...	# Clinical Investigation Priority Assessment Investigation Priority Statement The variant MAP2K2 p.Leu184Pro (ClinVar ID: 2086788) is assigned a Tier 1 — highest priority status within the unified RASopathy VUS Series pipeline. This designation indicates an elevated priority for further clinical investigation ...	VCV002086788	32	Definitive	2,086,788	broader_clingen_entity	MAP2K2	11	Tier 1 — highest priority	4	615280	MAP2K2 2086788 VCV002086788 ENSP00000262948.4:p.Leu184Pro 11 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615280 40496714 10.1016/j.gimo.2025.103430 2026-06-28 faeeeb495518	cardiofaciocutaneous syndrome	ENSP00000262948.4:p.Leu184Pro	faeeeb495518	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: SHOC2 Protein variant: ENSP00000358464.5:p.Leu194Phe ClinVar ID: 2724657 Investigation score: 12 CADD PHRED: 31.0 Concordant predictors: 5 Contextualize the gene–disease relationship ac...	The ENSP00000358464.5:p.Leu194Phe variant (ClinVar ID: 2724657) in SHOC2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 31.0, and support from 5 concordant computational predictor(s). Additiona...	# Task: Tier 1 Prioritization Analysis for Variant of Uncertain Significance (VUS) ## Instructions Based on the computational criteria and contextual data provided below, generate a detailed description of the Tier 1 prioritization for the specified Variant of Uncertain Significance (VUS). Your response must: 1....	# Tier 1 Prioritization Analysis: SHOC2 p.Leu194Phe ## Variant Identification * Gene: SHOC2 * Protein Variant: ENSP00000358464.5:p.Leu194Phe * ClinVar ID: 2724657 (VCV002724657) * Associated Condition: Noonan syndrome-like disorder with loose anagen hair (OMIM: 607721) ## 1. Analysis of Comput...	VCV002724657	31	Definitive	2,724,657	broader_clingen_entity	SHOC2	12	Tier 1 — highest priority	5	607721	SHOC2 2724657 VCV002724657 ENSP00000358464.5:p.Leu194Phe 12 Tier 1 — highest priority 31.0 5 Noonan syndrome-like disorder with loose anagen hair Definitive broader_clingen_entity 607721 40496714 10.1016/j.gimo.2025.103430 2026-06-28 a6db36e43218	Noonan syndrome-like disorder with loose anagen hair	ENSP00000358464.5:p.Leu194Phe	a6db36e43218	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: RIT1 Protein variant: ENSP00000357306.3:p.Ala77Gly ClinVar ID: 850519 Investigation score: 12 CADD PHRED: 32.0 Concordant predictors: 5 Clearly explain that Tier 1 represents a computational prior...	The ENSP00000357306.3:p.Ala77Gly variant (ClinVar ID: 850519) in RIT1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 32.0, and support from 5 concordant computational predictor(s). Additional p...	You are an expert clinical genetics analyst. Your task is to summarize the computational evidence level and gene–disease validity for the Variant of Uncertain Significance (VUS) detailed in the data block below. Definitions: - VUS (Variant of Uncertain Significance): A genetic change where the effect on healt...	Variant Prioritization Summary: RIT1 c.[Variant] p.Ala77Gly Variant Identification * Gene: RIT1 * Protein Change: ENSP00000357306.3:p.Ala77Gly * ClinVar Accession: VCV000850519 (ClinVar ID: 850519) * Associated Condition: Noonan syndrome (OMIM #615355) * Current Classification: ...	VCV000850519	32	Definitive	850,519	broader_clingen_entity	RIT1	12	Tier 1 — highest priority	5	615355	RIT1 850519 VCV000850519 ENSP00000357306.3:p.Ala77Gly 12 Tier 1 — highest priority 32.0 5 Noonan syndrome Definitive broader_clingen_entity 615355 40496714 10.1016/j.gimo.2025.103430 2026-06-28 17d8cdfd48de	Noonan syndrome	ENSP00000357306.3:p.Ala77Gly	17d8cdfd48de	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: BRAF Protein variant: ENSP00000493543.1:p.Ser637Leu ClinVar ID: 2123228 Investigation score: 12 CADD PHRED: 33.0 Concordant predictors: 4 Clearly explain that Tier 1 represents a computational pri...	The ENSP00000493543.1:p.Ser637Leu variant (ClinVar ID: 2123228) in BRAF was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additional...	# Task: Analyze Computational Evidence and Gene-Disease Validity Please summarize the computational evidence level and gene–disease validity for the Variant of Uncertain Significance (VUS) detailed below. Key Clarification: Explicitly state that "Tier 1" represents a high computational priority for review, not a...	### Computational Evidence Summary for BRAF c.1910C>T (p.Ser637Leu) Variant Identification * Gene: BRAF * Protein Change: ENSP00000493543.1:p.Ser637Leu * ClinVar Variation ID: 2123228 (VCV002123228) * Current Classification: Variant of Uncertain Significance (VUS) #### 1. Computational E...	VCV002123228	33	Definitive	2,123,228	broader_clingen_entity	BRAF	12	Tier 1 — highest priority	4	115150	BRAF 2123228 VCV002123228 ENSP00000493543.1:p.Ser637Leu 12 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 115150 40496714 10.1016/j.gimo.2025.103430 2026-06-28 d26aefb37d36	cardiofaciocutaneous syndrome	ENSP00000493543.1:p.Ser637Leu	d26aefb37d36	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: MAP2K2 Protein variant: ENSP00000262948.4:p.Arg193Gln ClinVar ID: 179899 Investigation score: 12 CADD PHRED: 33.0 Concordant predictors: 4 Clarify which additional evidence, including f...	The ENSP00000262948.4:p.Arg193Gln variant (ClinVar ID: 179899) in MAP2K2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additiona...	# Task: VUS Tier 1 Prioritization and Reclassification Analysis Based on the computational criteria and raw data provided below, perform the following two tasks regarding the Variant of Uncertain Significance (VUS): 1. Describe the Tier 1 Prioritization: Explain why this variant is classified as "Tier 1 — highest...	Variant Identification * Gene: MAP2K2 * Protein Change: ENSP00000262948.4:p.Arg193Gln * ClinVar ID: 179899 * Associated Condition: Cardiofaciocutaneous syndrome (OMIM: 615280) ### 1. Tier 1 Prioritization Rationale The classification of MAP2K2 p.Arg193Gln as "Tier 1 — highest priority" for...	VCV000179899	33	Definitive	179,899	broader_clingen_entity	MAP2K2	12	Tier 1 — highest priority	4	615280	MAP2K2 179899 VCV000179899 ENSP00000262948.4:p.Arg193Gln 12 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615280 40496714 10.1016/j.gimo.2025.103430 2026-06-28 9ffc4d5f276b	cardiofaciocutaneous syndrome	ENSP00000262948.4:p.Arg193Gln	9ffc4d5f276b	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Assess the clinical investigation priority of the following variant identified by the unified RASopathy VUS Series pipeline: Gene: BRAF Protein variant: ENSP00000493543.1:p.Gly469Glu ClinVar ID: 13974 Investigation score: 11 CADD PHRED: 32.0 Concordant predictors: 4 Contextualize the gene–disease relationship accordi...	The ENSP00000493543.1:p.Gly469Glu variant (ClinVar ID: 13974) in BRAF was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 32.0, and support from 4 concordant computational predictor(s). Additional p...	# Task: Clinical Investigation Priority Assessment Assess the clinical investigation priority of the variant identified by the unified RASopathy VUS (Variant of Uncertain Significance) Series pipeline using the data provided below. ## Instructions 1. Priority Assessment: Evaluate the variant's priority based on ...	# Clinical Investigation Priority Assessment ## Variant Identification * Gene: BRAF * Protein Variant: ENSP00000493543.1:p.Gly469Glu * ClinVar ID: 13974 ## 1. Priority Assessment Based on the provided metrics, this variant is assigned Tier 1 — highest priority for clinical investigation. The computa...	VCV000013974	32	Definitive	13,974	broader_clingen_entity	BRAF	11	Tier 1 — highest priority	4	115150	BRAF 13974 VCV000013974 ENSP00000493543.1:p.Gly469Glu 11 Tier 1 — highest priority 32.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 115150 40496714 10.1016/j.gimo.2025.103430 2026-06-28 b52e4a9354b6	cardiofaciocutaneous syndrome	ENSP00000493543.1:p.Gly469Glu	b52e4a9354b6	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Assess the clinical investigation priority of the following variant identified by the unified RASopathy VUS Series pipeline: Gene: MAP2K1 Protein variant: ENSP00000302486.5:p.Ser231Trp ClinVar ID: 2846662 Investigation score: 14 CADD PHRED: 36.0 Concordant predictors: 4 Clearly explain that Tier 1 represents a comput...	The ENSP00000302486.5:p.Ser231Trp variant (ClinVar ID: 2846662) in MAP2K1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 14, a CADD PHRED score of 36.0, and support from 4 concordant computational predictor(s). Addition...	# Task: Clinical Investigation Priority Assessment Assess the clinical investigation priority of the following variant identified by the unified RASopathy VUS (Variant of Uncertain Significance) Series pipeline. Critical Requirement: Clearly explain that "Tier 1" represents a computational priority for further r...	### Clinical Investigation Priority Assessment: MAP2K1 c.[Variant] p.Ser231Trp Variant Identification * Gene: MAP2K1 * Protein Change: p.Ser231Trp (ENSP00000302486.5) * ClinVar Variation ID: 2846662 (VCV002846662) * Associated Condition: Cardiofaciocutaneous Syndrome (CFC) #### 1. Comput...	VCV002846662	36	Definitive	2,846,662	broader_clingen_entity	MAP2K1	14	Tier 1 — highest priority	4	615279	MAP2K1 2846662 VCV002846662 ENSP00000302486.5:p.Ser231Trp 14 Tier 1 — highest priority 36.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615279 40496714 10.1016/j.gimo.2025.103430 2026-06-28 b2669264a613	cardiofaciocutaneous syndrome	ENSP00000302486.5:p.Ser231Trp	b2669264a613	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: RIT1 Protein variant: ENSP00000357306.3:p.Gly93Val ClinVar ID: 4614843 Investigation score: 11 CADD PHRED: 32.0 Concordant predictors: 5 Contextualize the gene–disease relationship acco...	The ENSP00000357306.3:p.Gly93Val variant (ClinVar ID: 4614843) in RIT1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 32.0, and support from 5 concordant computational predictor(s). Additional ...	# Task: VUS Tier 1 Prioritization and Gene-Disease Contextualization Based on the computational criteria and raw data provided below, perform the following analysis for the Variant of Uncertain Significance (VUS): 1. Tier 1 Prioritization Description: Describe the prioritization of this variant as "Tier 1 — highe...	### Variant Prioritization and Gene-Disease Contextualization Report Variant Identification * Gene: RIT1 * Protein Variant: ENSP00000357306.3:p.Gly93Val * ClinVar ID: 4614843 (VCV004614843) * Associated Condition: Noonan syndrome 1. Tier 1 Prioritization Description Based on the provided compu...	VCV004614843	32	Definitive	4,614,843	broader_clingen_entity	RIT1	11	Tier 1 — highest priority	5	615355	RIT1 4614843 VCV004614843 ENSP00000357306.3:p.Gly93Val 11 Tier 1 — highest priority 32.0 5 Noonan syndrome Definitive broader_clingen_entity 615355 40496714 10.1016/j.gimo.2025.103430 2026-06-28 976b4bf56458	Noonan syndrome	ENSP00000357306.3:p.Gly93Val	976b4bf56458	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: SHOC2 Protein variant: ENSP00000358464.5:p.Asn271Ser ClinVar ID: 4076674 Investigation score: 12 CADD PHRED: 27.9 Concordant predictors: 5 Contextualize the gene–disease relationship a...	The ENSP00000358464.5:p.Asn271Ser variant (ClinVar ID: 4076674) in SHOC2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 12, a CADD PHRED score of 27.9, and support from 5 concordant computational predictor(s). Additiona...	# Task: Analyze Computational Prioritization Data for Genetic Variant Analyze the provided computational prioritization data for the selected candidate variant intended for additional functional investigation. Specifically: 1. Data Review: Examine the variant's metrics, including the investigation score, CADD PHR...	### Computational Prioritization Analysis: SHOC2 p.Asn271Ser 1. Computational Evidence Review The candidate variant SHOC2 ENSP00000358464.5:p.Asn271Ser (ClinVar ID: 4076674) has been assigned the following computational metrics, reported exactly as provided: * Investigation Score: 12 * **CADD PHRED Sco...	VCV004076674	27.9	Definitive	4,076,674	broader_clingen_entity	SHOC2	12	Tier 1 — highest priority	5	607721	SHOC2 4076674 VCV004076674 ENSP00000358464.5:p.Asn271Ser 12 Tier 1 — highest priority 27.9 5 Noonan syndrome-like disorder with loose anagen hair Definitive broader_clingen_entity 607721 40496714 10.1016/j.gimo.2025.103430 2026-06-28 574b6cc9373a	Noonan syndrome-like disorder with loose anagen hair	ENSP00000358464.5:p.Asn271Ser	574b6cc9373a	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: RAF1 Protein variant: ENSP00000251849.4:p.Phe360Ser ClinVar ID: 981541 Investigation score: 13 CADD PHRED: 34.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context ...	The ENSP00000251849.4:p.Phe360Ser variant (ClinVar ID: 981541) in RAF1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 13, a CADD PHRED score of 34.0, and support from 4 concordant computational predictor(s). Additional ...	# Task: Computational Prioritization Analysis for RAF1 Variant Analyze the provided computational prioritization data for the selected candidate variant intended for additional functional investigation. ## Objectives 1. Contextual Analysis: Integrate ClinGen (Clinical Genome Resource) and GenCC (Gene Curation Co...	# Computational Prioritization Analysis: RAF1 p.Phe360Ser ## Variant Identification * Gene: RAF1 (HGNC:9829) * Protein Variant: ENSP00000251849.4:p.Phe360Ser * ClinVar Accession: 981541 (VCV000981541) * Associated Condition: Noonan syndrome (OMIM: 611553) ## Computational Evidence Reporting The follow...	VCV000981541	34	Definitive	981,541	exact	RAF1	13	Tier 1 — highest priority	4	611553	RAF1 981541 VCV000981541 ENSP00000251849.4:p.Phe360Ser 13 Tier 1 — highest priority 34.0 4 Noonan syndrome Definitive exact 611553 40496714 10.1016/j.gimo.2025.103430 2026-06-28 f86e148a01d9	Noonan syndrome	ENSP00000251849.4:p.Phe360Ser	f86e148a01d9	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Based on the computational criteria below, describe the Tier 1 prioritization of this variant of uncertain significance (VUS): Gene: MAP2K1 Protein variant: ENSP00000302486.5:p.Gly210Arg ClinVar ID: 1316067 Investigation score: 13 CADD PHRED: 33.0 Concordant predictors: 4 Clearly explain that Tier 1 represents a comp...	The ENSP00000302486.5:p.Gly210Arg variant (ClinVar ID: 1316067) in MAP2K1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 13, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Addition...	Based on the computational criteria provided below, describe the Tier 1 prioritization for the specified Variant of Uncertain Significance (VUS). Definitions: - VUS (Variant of Uncertain Significance): A genetic change whose impact on health is not yet known. - Tier 1: Indicates the highest computational ...	### Tier 1 Computational Prioritization Analysis: MAP2K1 c.[Variant] p.Gly210Arg Variant Identification * Gene: MAP2K1 * Protein Change: p.Gly210Arg (ENSP00000302486.5) * ClinVar Accession: VCV001316067 (Variation ID: 1316067) * Associated Condition: Cardiofaciocutaneous syndrome (CFC) #...	VCV001316067	33	Definitive	1,316,067	broader_clingen_entity	MAP2K1	13	Tier 1 — highest priority	4	615279	MAP2K1 1316067 VCV001316067 ENSP00000302486.5:p.Gly210Arg 13 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615279 40496714 10.1016/j.gimo.2025.103430 2026-06-28 56e5a010eb22	cardiofaciocutaneous syndrome	ENSP00000302486.5:p.Gly210Arg	56e5a010eb22	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: SOS1 Protein variant: ENSP00000384675.2:p.Phe464Ser ClinVar ID: 981564 Investigation score: 14 CADD PHRED: 33.0 Concordant predictors: 4 Clearly explain that Tier 1 represents a computational prio...	The ENSP00000384675.2:p.Phe464Ser variant (ClinVar ID: 981564) in SOS1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 14, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additional ...	# Task: Analyze Computational Evidence and Gene-Disease Validity for a Tier 1 VUS Please summarize the computational evidence level and gene–disease validity associated with the Variant of Uncertain Significance (VUS) detailed below. Important Clarification: Explicitly state that "Tier 1" represents a computatio...	### Computational Evidence Summary for SOS1 c.[Variant] p.Phe464Ser (VCV000981564) Computational Metrics Analysis The variant ENSP00000384675.2:p.Phe464Ser in the SOS1 gene is associated with the following computational evidence values derived from the provided input data: * CADD PHRED Score: 33.0. This va...	VCV000981564	33	Definitive	981,564	exact	SOS1	14	Tier 1 — highest priority	4	163950	SOS1 981564 VCV000981564 ENSP00000384675.2:p.Phe464Ser 14 Tier 1 — highest priority 33.0 4 Noonan syndrome Definitive exact 163950 40496714 10.1016/j.gimo.2025.103430 2026-06-28 47b23096d789	Noonan syndrome	ENSP00000384675.2:p.Phe464Ser	47b23096d789	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: SOS2 Protein variant: ENSP00000216373.5:p.Val336Asp ClinVar ID: 4709552 Investigation score: 11 CADD PHRED: 27.1 Concordant predictors: 5 Contextualize the gene–disease relationship according to C...	The ENSP00000216373.5:p.Val336Asp variant (ClinVar ID: 4709552) in SOS2 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 27.1, and support from 5 concordant computational predictor(s). Additional...	Summarize the computational evidence level and gene–disease validity for the following Tier 1 Variant of Uncertain Significance (VUS). Additionally, contextualize the gene–disease relationship according to ClinGen standards, explicitly noting any differences in disease-entity specificity or MONDO (Monarch Disease Ontol...	Variant Identification * Gene: SOS2 * Protein Change: ENSP00000216373.5:p.Val336Asp * ClinVar Variation ID: 4709552 (VCV004709552) * Current Classification: Variant of Uncertain Significance (VUS) * Prioritization Tier: Tier 1 (Highest Computational Priority) **Computational Evidence Assessme...	VCV004709552	27.1	Definitive	4,709,552	broader_clingen_entity	SOS2	11	Tier 1 — highest priority	5	616559	SOS2 4709552 VCV004709552 ENSP00000216373.5:p.Val336Asp 11 Tier 1 — highest priority 27.1 5 Noonan syndrome Definitive broader_clingen_entity 616559 40496714 10.1016/j.gimo.2025.103430 2026-06-28 6168fabbf1d3	Noonan syndrome	ENSP00000216373.5:p.Val336Asp	6168fabbf1d3	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Assess the clinical investigation priority of the following variant identified by the unified RASopathy VUS Series pipeline: Gene: SOS1 Protein variant: ENSP00000384675.2:p.Arg497Pro ClinVar ID: 934560 Investigation score: 14 CADD PHRED: 33.0 Concordant predictors: 4 Include the ClinGen and GenCC validity context and...	The ENSP00000384675.2:p.Arg497Pro variant (ClinVar ID: 934560) in SOS1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 14, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additional ...	# Clinical Investigation Priority Assessment Evaluate the clinical investigation priority for the following Variant of Uncertain Significance (VUS) identified by the unified RASopathy pipeline. Definitions: - VUS: Variant of Uncertain Significance. - ACMG/AMP: American College of Medical Genetics and Gen...	# Clinical Investigation Priority Assessment Variant: SOS1 ENSP00000384675.2:p.Arg497Pro (ClinVar ID: 934560) Phenotype: Noonan syndrome ## 1. Contextual Validation The gene–disease relationship between SOS1 and Noonan syndrome is classified as Definitive by ClinGen GCEP, with an exact condition ...	VCV000934560	33	Definitive	934,560	exact	SOS1	14	Tier 1 — highest priority	4	163950	SOS1 934560 VCV000934560 ENSP00000384675.2:p.Arg497Pro 14 Tier 1 — highest priority 33.0 4 Noonan syndrome Definitive exact 163950 40496714 10.1016/j.gimo.2025.103430 2026-06-28 add8d73541c9	Noonan syndrome	ENSP00000384675.2:p.Arg497Pro	add8d73541c9	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Summarize the computational evidence level and gene–disease validity associated with this VUS classified as Tier 1: Gene: HRAS Protein variant: p.Gly13Val ClinVar ID: 180848 Investigation score: 8 CADD PHRED: 23.4 Concordant predictors: 3 Clarify which additional evidence, including functional studies, segregation da...	The p.Gly13Val variant (ClinVar ID: 180848) in HRAS was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 8, a CADD PHRED score of 23.4, and support from 3 concordant computational predictor(s). Additional pipeline evidence: l...	# Task: Genetic Variant Evidence Analysis You are an expert genetic counselor and clinical genomicist. Analyze the provided Variant of Uncertain Significance (VUS) data to evaluate its current classification and identify requirements for reclassification. ## Instructions 1. Evidence Summary: Based on the data be...	# Genetic Variant Evidence Analysis Variant: HRAS c.38G>T (p.Gly13Val) ClinVar ID: 180848 (VCV000180848) ## 1. Evidence Summary ### Computational Evidence The current computational assessment for this variant is based on the following in silico metrics provided in the investigation data: * **CADD PHRED...	VCV000180848	23.4	Definitive	180,848	exact	HRAS	8	Tier 1 — highest priority	3	218040	HRAS 180848 VCV000180848 p.Gly13Val 8 Tier 1 — highest priority 23.4 3 Costello syndrome Definitive exact 218040 40496714 10.1016/j.gimo.2025.103430 2026-06-28 3128c77ceb69	Costello syndrome	p.Gly13Val	3128c77ceb69	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00
Analyze the computational prioritization data for this variant selected as a candidate for additional functional investigation: Gene: MAP2K1 Protein variant: ENSP00000302486.5:p.Gly80Ser ClinVar ID: 1440001 Investigation score: 11 CADD PHRED: 33.0 Concordant predictors: 4 Clarify which additional evidence, including ...	The ENSP00000302486.5:p.Gly80Ser variant (ClinVar ID: 1440001) in MAP2K1 was classified as Tier 1 — the highest investigation priority — by the unified RASopathy VUS Series pipeline. It received an investigation score of 11, a CADD PHRED score of 33.0, and support from 4 concordant computational predictor(s). Additiona...	# Task: Analyze Computational Prioritization Data for Genetic Variant Reclassification You are an expert geneticist and variant curator. Analyze the provided computational prioritization data for a specific gene variant selected as a candidate for additional functional investigation. Based on this data, clarify exactl...	### Variant Prioritization Analysis: MAP2K1 p.Gly80Ser Variant Identification and Computational Metrics The variant under review is MAP2K1 p.Gly80Ser (ENSP00000302486.5:p.Gly80Ser; ClinVar ID: 1440001; VCV: VCV001440001). The following computational prioritization metrics have been recorded for this candidate:...	VCV001440001	33	Definitive	1,440,001	broader_clingen_entity	MAP2K1	11	Tier 1 — highest priority	4	615279	MAP2K1 1440001 VCV001440001 ENSP00000302486.5:p.Gly80Ser 11 Tier 1 — highest priority 33.0 4 cardiofaciocutaneous syndrome Definitive broader_clingen_entity 615279 40496714 10.1016/j.gimo.2025.103430 2026-06-28 0c47e324ecb6	cardiofaciocutaneous syndrome	ENSP00000302486.5:p.Gly80Ser	0c47e324ecb6	10.1016/j.gimo.2025.103430	40496714	2026-06-28T00:00:00

End of preview. Expand in Data Studio

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

adaption-rasopathy_vus_tier1_reports

This dataset contains structured clinical reports for Tier 1 prioritized variants of uncertain significance (VUS) within RASopathy-associated genes like PTPN11, SOS1, and RAF1. Each entry details computational evidence metrics, including investigation scores and CADD PHRED values, alongside ClinGen gene-disease validity classifications. The reports explicitly clarify that Tier 1 status indicates high priority for functional investigation rather than a final ACMG/AMP clinical reclassification.