ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.905C>T (p.Ala302Val)

gnomAD frequency: 0.00001  dbSNP: rs1418676444
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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 RCV001338690 SCV001532376 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-24 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 302 of the BRCA1 protein (p.Ala302Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant has not been reported in the literature in individuals with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV002447393 SCV002682885 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-12 criteria provided, single submitter clinical testing The p.A302V variant (also known as c.905C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 905. The alanine at codon 302 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV002447393 SCV003846299 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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