Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212503 | SCV001384088 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-02-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 430 of the BRIP1 protein (p.Ile430Val). 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: 929536). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002379752 | SCV002691547 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-03 | criteria provided, single submitter | clinical testing | The p.I430V variant (also known as c.1288A>G), located in coding exon 8 of the BRIP1 gene, results from an A to G substitution at nucleotide position 1288. The isoleucine at codon 430 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported with a carrier frequency of 0.00008 in 12366 male controls of Japanese ancestry and was not observed in 7636 unselected prostate cancer patients (Momozawa Y et al. J Natl Cancer Inst, 2020 04;112:369-376). This amino acid position is highly 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. |
| Leiden Open Variation Database | RCV001194743 | SCV001364517 | uncertain significance | not provided | 2019-08-13 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. |