Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820808 | SCV000961537 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with arginine at codon 342 of the BRIP1 protein (p.Ser342Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. 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 BRIP1-related disease. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV001017050 | SCV001178073 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-16 | criteria provided, single submitter | clinical testing | The p.S342R variant (also known as c.1024A>C), located in coding exon 7 of the BRIP1 gene, results from an A to C substitution at nucleotide position 1024. The serine at codon 342 is replaced by arginine, an amino acid with dissimilar 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. |