ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4954A>T (p.Met1652Leu)

dbSNP: rs1348949389
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695271 SCV000823759 uncertain significance Hereditary breast ovarian cancer syndrome 2018-05-10 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 1652 of the BRCA1 protein (p.Met1652Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV001023316 SCV001185175 likely benign Hereditary cancer-predisposing syndrome 2019-07-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Brotman Baty Institute, University of Washington RCV001077350 SCV001243264 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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