Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569160 | SCV000668883 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.I365L variant (also known as c.1093A>C), located in coding exon 7 of the BRIP1 gene, results from an A to C substitution at nucleotide position 1093. The isoleucine at codon 365 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is poorly 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 |
RCV001226561 | SCV001398881 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-07-26 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 483146). 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 isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 365 of the BRIP1 protein (p.Ile365Leu). 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. 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. |
| Gene |
RCV001764660 | SCV002008681 | uncertain significance | not provided | 2020-02-27 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV004569200 | SCV005059956 | uncertain significance | Familial cancer of breast | 2023-11-13 | criteria provided, single submitter | clinical testing |