Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001027247 | SCV001189774 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-05 | criteria provided, single submitter | clinical testing | The p.M273V variant (also known as c.817A>G), located in coding exon 6 of the BRIP1 gene, results from an A to G substitution at nucleotide position 817. The methionine at codon 273 is replaced by valine, an amino acid with highly similar properties. This variant was identified in a cohort of 882 Chinese individuals with a personal and/or family history of breast or ovarian cancers who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This amino acid position is highly 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 | RCV001225541 | SCV001397824 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 273 of the BRIP1 protein (p.Met273Val). The methionine residue is highly 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 affected with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |