Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000637452 | SCV000758911 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2017-12-20 | 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. This sequence change replaces methionine with valine at codon 192 of the BRCA2 protein (p.Met192Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
Ambry Genetics | RCV002343245 | SCV002650702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-12 | criteria provided, single submitter | clinical testing | The p.M192V variant (also known as c.574A>G), located in coding exon 6 of the BRCA2 gene, results from an A to G substitution at nucleotide position 574. The methionine at codon 192 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |