ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3785C>T (p.Ser1262Leu)

dbSNP: rs80358620
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002022530 SCV002295895 uncertain significance Hereditary breast ovarian cancer syndrome 2021-04-23 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with leucine at codon 1262 of the BRCA2 protein (p.Ser1262Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine.
Ambry Genetics RCV002346275 SCV002620455 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-09 criteria provided, single submitter clinical testing The p.S1262L variant (also known as c.3785C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3785. The serine at codon 1262 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 RCV002346275 SCV003846874 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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