Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000575692 | SCV000666239 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | The p.E675A variant (also known as c.2024A>C), located in coding exon 13 of the BRIP1 gene, results from an A to C substitution at nucleotide position 2024. The glutamic acid at codon 675 is replaced by alanine, an amino acid with dissimilar 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. |
Labcorp Genetics |
RCV001867861 | SCV002177017 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 675 of the BRIP1 protein (p.Glu675Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with prostate cancer and in unaffected controls (PMID: 31214711). ClinVar contains an entry for this variant (Variation ID: 481653). 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. |
Leiden Open Variation Database | RCV001194765 | SCV001364548 | uncertain significance | not provided | 2019-08-13 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. |