Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220033 | SCV000277716 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | The p.V588M variant (also known as c.1762G>A), located in coding exon 11 of the BRIP1 gene, results from a G to A substitution at nucleotide position 1762. The valine at codon 588 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well 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 p.V588M remains unclear. |
Labcorp Genetics |
RCV000527441 | SCV000633573 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-11-09 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 233362). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 588 of the BRIP1 protein (p.Val588Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. |