Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001340905 | SCV001534739 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with glycine at codon 289 of the BRIP1 protein (p.Val289Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV003294335 | SCV003998214 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-25 | criteria provided, single submitter | clinical testing | The p.V289G variant (also known as c.866T>G), located in coding exon 6 of the BRIP1 gene, results from a T to G substitution at nucleotide position 866. The valine at codon 289 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |