Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570177 | SCV000661516 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-26 | criteria provided, single submitter | clinical testing | The p.K503N variant (also known as c.1509A>C), located in coding exon 10 of the BRIP1 gene, results from an A to C substitution at nucleotide position 1509. The lysine at codon 503 is replaced by asparagine, an amino acid with similar properties. This amino acid position is 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. |
| Labcorp Genetics |
RCV000798722 | SCV000938352 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 503 of the BRIP1 protein (p.Lys503Asn). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 479423). 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 not expected to disrupt BRIP1 protein function with a negative predictive value of 80%. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800765 | SCV002047201 | uncertain significance | not specified | 2021-05-28 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569097 | SCV005059270 | uncertain significance | Familial cancer of breast | 2024-01-31 | criteria provided, single submitter | clinical testing |