ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.766A>T (p.Arg256Trp)

dbSNP: rs587781833
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130123 SCV000184955 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-17 criteria provided, single submitter clinical testing The p.R256W variant (also known as c.766A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 766. The arginine at codon 256 is replaced by tryptophan, an amino acid with dissimilar properties. Based on protein sequence alignment, 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.
Invitae RCV000474139 SCV000549382 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 256 of the BRCA1 protein (p.Arg256Trp). 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: 141549). 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 RCV000130123 SCV003847960 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).
BRCAlab, Lund University RCV003493454 SCV004244146 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided clinical testing

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