ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1187A>T (p.Asp396Val)

dbSNP: rs1555592280
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773824 SCV000907524 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773824 SCV002633818 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-15 criteria provided, single submitter clinical testing The p.D396V variant (also known as c.1187A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1187. The aspartic acid at codon 396 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is not 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002536662 SCV003319774 uncertain significance Hereditary breast ovarian cancer syndrome 2022-02-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 396 of the BRCA1 protein (p.Asp396Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 629134). 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. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000773824 SCV003846119 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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