ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1799T>G (p.Val600Gly)

dbSNP: rs113488022
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000798913 SCV001424737 pathogenic RASopathy 2020-06-25 reviewed by expert panel curation The c.1799T>G (p.Val600Gly) variant in BRAF is absent from gnomAD (PM2). It has been identified in one individual with Cardiofaciocutaneous syndrome (PS4_Supporting; PMID: 20735442). It has also been reported in the literature as an unconfirmed de novo occurrence (PM6; GeneDx internal communication). In vitro functional studies provide some evidence that the p.Val600Gly variant may impact protein function (PS3; PMID: 20735442). Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of BRAF (PM1; PMID 29493581). Computational prediction tools and conservation analysis suggest that the p.Val600Gly variant may impact the protein (PP3). Finally, the variant is located in BRAF, 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): PS3, PM1, PM2, PM6, PS4_Supporting, PP3, PP2.
Invitae RCV000798913 SCV000938556 pathogenic RASopathy 2021-08-27 criteria provided, single submitter clinical testing
GeneReviews RCV000208774 SCV000264637 pathogenic Cardio-facio-cutaneous syndrome 2016-03-03 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433794 SCV000504247 pathogenic Melanoma 2014-10-02 no assertion criteria provided literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354831 SCV001549542 uncertain significance not provided no assertion criteria provided clinical testing
PerkinElmer Genomics RCV001354831 SCV002022062 likely pathogenic not provided 2020-05-04 no assertion criteria provided clinical testing

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