ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1131G>C (p.Glu377Asp) (rs777845659)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166252 SCV000217032 uncertain significance Hereditary cancer-predisposing syndrome 2014-10-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000560741 SCV000635142 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-04-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 377 of the BRCA2 protein (p.Glu377Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs777845659, ExAC 0.02%) but has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 186628). 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 aspartic acid 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758859 SCV000887747 uncertain significance not provided 2018-01-05 criteria provided, single submitter clinical testing

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