Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215748 | SCV000275402 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-17 | criteria provided, single submitter | clinical testing | The p.I833V variant (also known as c.2497A>G), located in coding exon 17 of the BRIP1 gene, results from an A to G substitution at nucleotide position 2497. The isoleucine at codon 833 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Mendelics | RCV000709539 | SCV000839366 | uncertain significance | Fanconi anemia complementation group J | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000989993 | SCV001140755 | uncertain significance | Familial cancer of breast | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001051764 | SCV001215940 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 833 of the BRIP1 protein (p.Ile833Val). 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: 231526). 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. |