Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001297542 | SCV001486566 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2020-04-14 | 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. 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 disruptive, 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 619 of the BRIP1 protein (p.Pro619Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV002411949 | SCV002719138 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | The p.P619S variant (also known as c.1855C>T), located in coding exon 12 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1855. The proline at codon 619 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |