ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1285T>A (p.Leu429Ile)

dbSNP: rs1555281818
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000533427 SCV000635154 uncertain significance Hereditary breast ovarian cancer syndrome 2017-02-05 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. This sequence change replaces leucine with isoleucine at codon 429 of the BRCA2 protein (p.Leu429Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. 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 isoleucine 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 novel 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157636 SCV003849971 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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