ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1781A>G (p.Asp594Gly)

dbSNP: rs121913338
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Total submissions: 13
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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 RCV000037932 SCV000061597 pathogenic Non-small cell lung carcinoma 2012-06-11 criteria provided, single submitter clinical testing This variant has been reported as a somatic change in large intestine, skin, end ometrium, stomach, and ovary (COSMIC, Fransen 2004) and has been observed in up to 11% of BRAF mutant positive lung adenocarcinoma (Paik 2011).
Invitae RCV001238853 SCV001411685 uncertain significance RASopathy 2021-08-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 594 of the BRAF protein (p.Asp594Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 13972). 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. Experimental studies have shown that this variant affects BRAF function (PMID: 23352452, 29595366). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000015006 SCV000035262 pathogenic Non-Hodgkin lymphoma 2003-11-17 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443882 SCV000504291 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423919 SCV000504292 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433779 SCV000504293 likely pathogenic Adrenal cortex carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443065 SCV000504294 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426339 SCV000504295 pathogenic Melanoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437006 SCV000504296 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442759 SCV000504297 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426107 SCV000504298 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435875 SCV000504299 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418680 SCV000504300 likely pathogenic B-cell chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only

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