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

dbSNP: rs121913338

Total submissions: 14

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).
Labcorp Genetics (formerly Invitae), Labcorp	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
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University	RCV000426107	SCV004042818	likely pathogenic	Lung adenocarcinoma		no assertion criteria provided	clinical testing