Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001227431 | SCV001399790 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-10-27 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 525 of the BRCA1 protein (p.Val525Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. |
Ambry Genetics | RCV002402711 | SCV002704091 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-31 | criteria provided, single submitter | clinical testing | The p.V525L variant (also known as c.1573G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1573. The valine at codon 525 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
University of Washington Department of Laboratory Medicine, |
RCV002402711 | SCV003851198 | 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). |