Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002025758 | SCV002294032 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-11-12 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 254 of the BRIP1 protein (p.Lys254Arg). |
| Ambry Genetics | RCV004046092 | SCV005029213 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | The p.K254R variant (also known as c.761A>G), located in coding exon 6 of the BRIP1 gene, results from an A to G substitution at nucleotide position 761. The lysine at codon 254 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |