ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2291T>C (p.Val764Ala)

gnomAD frequency: 0.00001  dbSNP: rs1234701709
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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 RCV001911179 SCV002158846 uncertain significance Hereditary breast ovarian cancer syndrome 2021-11-13 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. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 764 of the BRCA1 protein (p.Val764Ala).
Ambry Genetics RCV002458742 SCV002738092 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-14 criteria provided, single submitter clinical testing The p.V764A variant (also known as c.2291T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2291. The valine at codon 764 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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 RCV002458742 SCV003847783 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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