ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1477A>C (p.Ile493Leu)

dbSNP: rs2053933371
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001062021 SCV001226790 uncertain significance Hereditary breast ovarian cancer syndrome 2020-01-15 criteria provided, single submitter clinical testing 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. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 493 of the BRCA1 protein (p.Ile493Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine.
Ambry Genetics RCV002393303 SCV002700699 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-18 criteria provided, single submitter clinical testing The p.I493L variant (also known as c.1477A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide position 1477. The isoleucine at codon 493 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002393303 SCV003851269 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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