ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1336A>G (p.Arg446Gly) (rs587781715)

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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 RCV000129893 SCV000184710 uncertain significance Hereditary cancer-predisposing syndrome 2014-02-05 criteria provided, single submitter clinical testing Insufficient evidence
PreventionGenetics,PreventionGenetics RCV000679680 SCV000806893 uncertain significance not provided 2017-01-10 criteria provided, single submitter clinical testing
Invitae RCV000695651 SCV000824163 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-01-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 446 of the BRCA1 protein (p.Arg446Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. 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. ClinVar contains an entry for this variant (Variation ID: 141392). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The glycine 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.

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