ClinVar Miner

Submissions for variant NM_001374258.1(BRAF):c.1903T>C (p.Phe635Leu) (rs794729219)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414439 SCV000491004 pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing The c.1783T>C F595L missense variant in the BRAF gene has been reported previously in association with Cardio-Facio-Cutaneous (CFC) syndrome (Ciara et al., 2015). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. F595L is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Other F595L variants due to different nucleotide changes (c.1785T>A, c.1785T>G) as well as missense variants in nearby residues (N580D, N581D, G596V, L597V, T599A) have been reported in the Human Gene Mutation Database in association with BRAF-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. This amino acid substitution occurs at a highly conserved residue of the protein.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000184039 SCV000781087 likely pathogenic Cardiofaciocutaneous syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Mendelics RCV000184039 SCV000236570 pathogenic Cardiofaciocutaneous syndrome 1 2013-11-06 no assertion criteria provided clinical testing
Database of Curated Mutations (DoCM) RCV000427091 SCV000505590 likely pathogenic Cutaneous melanoma 2015-07-14 no assertion criteria provided literature only

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