Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000796962 | SCV000936498 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 520 of the BRIP1 protein (p.Ser520Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. 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: "Deleterious"; PolyPhen-2: "Probably 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 | RCV001012158 | SCV001172579 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-28 | criteria provided, single submitter | clinical testing | The p.S520N variant (also known as c.1559G>A), located in coding exon 10 of the BRIP1 gene, results from a G to A substitution at nucleotide position 1559. The serine at codon 520 is replaced by asparagine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |