Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001238396 | SCV001411202 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2020-07-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 1092 of the BRIP1 protein (p.Pro1092Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. 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. 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 | RCV003294127 | SCV003998208 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-18 | criteria provided, single submitter | clinical testing | The p.P1092T variant (also known as c.3274C>A), located in coding exon 19 of the BRIP1 gene, results from a C to A substitution at nucleotide position 3274. The proline at codon 1092 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |