Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001206370 | SCV001377676 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-22 | criteria provided, single submitter | clinical testing | 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: 937374). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs754398271, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 523 of the BRCA1 protein (p.Leu523Val). |
Ambry Genetics | RCV002402598 | SCV002708771 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-24 | criteria provided, single submitter | clinical testing | The p.L523V variant (also known as c.1567T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 1567. The leucine at codon 523 is replaced by valine, an amino acid with highly similar properties. 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. |
University of Washington Department of Laboratory Medicine, |
RCV002402598 | SCV003851204 | 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). |