ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1781A>T (p.Asp594Val)

dbSNP: rs121913338
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000796335 SCV001424741 pathogenic RASopathy 2020-05-18 reviewed by expert panel curation The c.1781A>T (p.Asp594Val) variant in BRAF was absent from large population studies (PM2; gnomAD, The variant has been reported in 3 probands with clinical features of a RASopathy (PS4_Moderate; SCV000935844.1, SCV000965957.1, GeneDx internal data). In one proband, the variant was reported as de novo with confirmed parentage (PS2). The c.1781A>T (p.Asp594Val) variant is located in the CR3 activation segment of BRAF, which has been defined by the ClinGen RASopathy Expert Panel as a region important for protein function (PM1; PMID 29493581). Computational prediction tools and conservation analysis suggest that the variant may impact protein function (PP3). Finally, c.1781A>T (p.Asp594Val) is located in the BRAF gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581). In summary, this variant meets criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PS2, PS4_Moderate, PM1, PM2, PP2, PP3,
Invitae RCV000796335 SCV000935844 uncertain significance RASopathy 2021-09-01 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000421094 SCV000504289 pathogenic Neoplasm of the large intestine 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434803 SCV000504290 pathogenic Melanoma 2015-07-14 no assertion criteria provided literature only
Service de Génétique Moléculaire,Hôpital Robert Debré RCV000824925 SCV000965957 uncertain significance Cardio-facio-cutaneous syndrome no assertion criteria provided clinical testing

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