ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2816T>C (p.Val939Ala)

dbSNP: rs1555588894
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000637329 SCV000758781 uncertain significance Hereditary breast ovarian cancer syndrome 2021-03-08 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 939 of the BRCA1 protein (p.Val939Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). 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 disease.
Color Diagnostics, LLC DBA Color Health RCV000773237 SCV000906849 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773237 SCV001177650 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-14 criteria provided, single submitter clinical testing The p.V939A variant (also known as c.2816T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2816. The valine at codon 939 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly 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.
Baylor Genetics RCV001294024 SCV001482784 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2019-08-24 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001766361 SCV001990428 uncertain significance not provided 2019-07-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
University of Washington Department of Laboratory Medicine, University of Washington RCV000773237 SCV003849331 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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