Submissions for variant NM_004333.6(BRAF):c.1600G>C (p.Gly534Arg)

dbSNP: rs180177041

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000015014	SCV000680156	pathogenic	Cardiofaciocutaneous syndrome 1	2017-09-08	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000208775	SCV000710865	likely pathogenic	Cardio-facio-cutaneous syndrome	2016-07-01	criteria provided, single submitter	clinical testing	The p.Gly534Arg variant in BRAF has been previously identified in one individual with clinical features of a RASopathy and occurred de novo (Rauen 2006, Gripp 2 007). It is absent from large population studies. Computational prediction too ls and conservation analysis suggest that this variant may impact the protein, t hough this information is not predictive enough to determine pathogenicity. In s ummary, although additional studies are required to fully establish its clinical significance, the p.Gly534Arg variant is likely pathogenic.
Ambry Genetics	RCV000623633	SCV000742637	likely pathogenic	Inborn genetic diseases	2017-07-11	criteria provided, single submitter	clinical testing
3billion	RCV000015014	SCV002012051	pathogenic	Cardiofaciocutaneous syndrome 1	2021-10-02	criteria provided, single submitter	clinical testing	Same nucleotide change resulting in same amino acid change has been previously reported as de novoo in similarly affected individual (PMID:23875798, 17551924, PS2). The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.942, 3Cnet: 0.998, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM	RCV000015014	SCV000035270	pathogenic	Cardiofaciocutaneous syndrome 1	2006-08-01	no assertion criteria provided	literature only
GeneReviews	RCV000208775	SCV000264634	not provided	Cardio-facio-cutaneous syndrome		no assertion provided	literature only
Dobyns Lab, Seattle Children's Research Institute	RCV000779634	SCV000916311	pathogenic	PHACE syndrome; Tethered cord; Genetic syndrome with a Dandy-Walker malformation as major feature	2019-02-18	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257953	SCV001434766	likely pathogenic	Dandy-Walker syndrome		no assertion criteria provided	research