Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002620504 | SCV003506190 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-05-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 473 of the BRIP1 protein (p.Met473Ile). This variant is not present in population databases (gnomAD no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV004070501 | SCV005029178 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | The p.M473I variant (also known as c.1419G>T), located in coding exon 9 of the BRIP1 gene, results from a G to T substitution at nucleotide position 1419. The methionine at codon 473 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |