Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002037321 | SCV002114666 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 389 of the BRIP1 protein (p.Val389Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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. |
| Ambry Genetics | RCV002329777 | SCV002627198 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-22 | criteria provided, single submitter | clinical testing | The p.V389L variant (also known as c.1165G>C), located in coding exon 8 of the BRIP1 gene, results from a G to C substitution at nucleotide position 1165. The valine at codon 389 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not 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. |