ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1460T>G (p.Val487Gly)

dbSNP: rs397516893
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037922 SCV000061585 likely pathogenic Cardio-facio-cutaneous syndrome 2012-04-13 criteria provided, single submitter clinical testing The Val487Gly variant in BRAF has been identified in one individual with Cardio- Facio-Cutaneous (CFC) syndrome and was absent in 210 Caucasian control chromosom es (Narumi 2007). Valine (Val) at position 487 is highly conserved across evolut ionarily distant species, increasing the likelihood that the change would not be tolerated. Computational analyses (biochemical amino acid properties, conservat ion, AlignGVGD, PolyPhen2 and SIFT) suggest that the Val487Gly variant may impac t the protein, though this information is not predictive enough to determine pat hogenicity. In summary, this variant is likely to be pathogenic, though segregat ion studies and functional analyses are required to fully establish the pathogen icity of this variant.
Ambry Genetics RCV000622585 SCV000740925 pathogenic Inborn genetic diseases 2015-05-29 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000788814 SCV000928070 pathogenic not provided 2018-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000788814 SCV002008924 pathogenic not provided 2021-01-19 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26795593, 17366577, 24719372, 18470943, 18413255, 33482860, 24803665)
Labcorp Genetics (formerly Invitae), Labcorp RCV001852794 SCV002196994 pathogenic RASopathy 2021-07-21 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRAF protein function. ClinVar contains an entry for this variant (Variation ID: 44806). This variant has been observed in individuals with BRAF-related conditions (PMID: 17366577, 22495831, 24719372, 26795593). This sequence change replaces valine with glycine at codon 487 of the BRAF protein (p.Val487Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine.

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