ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1391G>T (p.Gly464Val) (rs121913348)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000442182 SCV000505048 likely pathogenic Neoplasm 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426199 SCV000505049 likely pathogenic Neoplasm of the breast 2015-07-14 no assertion criteria provided literature only
Invitae RCV000033302 SCV000288405 likely pathogenic Rasopathy 2016-01-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 464 of the BRAF protein (p.Gly464Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with cardio-facio-cutaneous syndrome (PMID: 18413255, 18039235, 2102266). ClinVar contains an entry for this variant (Variation ID: 40364). Experimental studies have shown that this missense change disrupts BRAF inhibition, resulting in a constitutively active protein (PMID: 23907581, 19376813, 23680146, 25155755). In summary, this missense change results in a constitutively activity protein and is reported in affected individuals. While this variant is likely to be pathogenic, additional genetic data is needed to prove that conclusively. Therefore, it has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037914 SCV000061576 pathogenic Non-small cell lung cancer 2011-05-03 criteria provided, single submitter clinical testing Somatic BRAF variants have been identified in up to 3% of cases of lung adenocar cinoma (Davies 2002).

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