Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001923349 | SCV002184397 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-03-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1412636). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 724 of the BRIP1 protein (p.Ile724Thr). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Ambry Genetics | RCV002423033 | SCV002725338 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing | The p.I724T variant (also known as c.2171T>C), located in coding exon 14 of the BRIP1 gene, results from a T to C substitution at nucleotide position 2171. The isoleucine at codon 724 is replaced by threonine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |