ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1036C>G (p.Pro346Ala) (rs80357015)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695469 SCV000823971 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-13 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 346 of the BRCA1 protein (p.Pro346Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. 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 alanine 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759484 SCV000888828 uncertain significance not provided 2018-07-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017092 SCV001178118 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-11 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV001017092 SCV001345889 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-30 criteria provided, single submitter clinical testing

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