ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2203C>G (p.Leu735Val)

dbSNP: rs587781781
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130031 SCV000184857 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-29 criteria provided, single submitter clinical testing The p.L735V variant (also known as c.2203C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2203. The leucine at codon 735 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000637351 SCV000758805 uncertain significance Hereditary breast ovarian cancer syndrome 2023-01-16 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 141481). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 735 of the BRCA1 protein (p.Leu735Val).
Color Diagnostics, LLC DBA Color Health RCV000130031 SCV000912041 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199912 SCV001370679 uncertain significance not specified 2020-05-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2203C>G (p.Leu735Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250714 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2203C>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV001560449 SCV001782865 uncertain significance not provided 2019-09-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Also known as 2322C>G
University of Washington Department of Laboratory Medicine, University of Washington RCV000130031 SCV003847857 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).
All of Us Research Program, National Institutes of Health RCV003997542 SCV004818217 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2023-05-31 criteria provided, single submitter clinical testing

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