ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5246C>T (p.Pro1749Leu) (rs80357462)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000637542 SCV000759006 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1749 of the BRCA1 protein (p.Pro1749Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Pro1749Arg) has been shown to affect BRCA1 protein function (PMID: 21922593, 20516115, 28781887). 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.
Brotman Baty Institute,University of Washington RCV001072564 SCV001237974 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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