Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000232199 | SCV000288758 | uncertain significance | BAP1-related tumor predisposition syndrome | 2016-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with alanine at codon 209 of the BAP1 protein (p.Val209Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BAP1-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001775701 | SCV002012799 | uncertain significance | not provided | 2019-09-23 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002365197 | SCV002656535 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-31 | criteria provided, single submitter | clinical testing | The p.V209A variant (also known as c.626T>C), located in coding exon 8 of the BAP1 gene, results from a T to C substitution at nucleotide position 626. The valine at codon 209 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |