Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001373567 | SCV001570287 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 255 of the BRIP1 protein (p.Gln255Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1063703). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRIP1 protein function. 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. |
Sema4, |
RCV002259111 | SCV002529231 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-15 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002259111 | SCV005101018 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-10 | criteria provided, single submitter | clinical testing | The p.Q255P variant (also known as c.764A>C), located in coding exon 6 of the BRIP1 gene, results from an A to C substitution at nucleotide position 764. The glutamine at codon 255 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |