Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167147 | SCV000217977 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-19 | criteria provided, single submitter | clinical testing | The p.V271L variant (also known as c.811G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 811. The valine at codon 271 is replaced by leucine, an amino acid with highly similar properties. This alteration has been observed in individuals with personal and/or family history of breast and/or ovarian cancer (Wárlám-Rodenhuis CC et al. Eur. J. Cancer, 2005 Jul;41:1409-15; Lu W et al. Fam. Cancer, 2012 Sep;11:381-5). In addition, this variant had near wildtype function in a homology-directed-repair and cisplatin-sensitivity assay, however, this could not be confirmed by statistical analysis (Bouwman P et al. Cancer Discov, 2013 Oct;3:1142-55). This amino acid position is well 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. |
Invitae | RCV000689692 | SCV000817355 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-08-21 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 23867111, 25823446). 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. ClinVar contains an entry for this variant (Variation ID: 187421). This missense change has been observed in individual(s) with a strong family history of breast and/or ovarian cancer and breast cancer (PMID: 15955690, 22476429). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 271 of the BRCA1 protein (p.Val271Leu). |
University of Washington Department of Laboratory Medicine, |
RCV000167147 | SCV003847922 | 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). |