Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000629983 | SCV000750939 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-11-16 | 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 disruptive, 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 PMS2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 215 of the PMS2 protein (p.Val215Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. |
| Ambry Genetics | RCV002360497 | SCV002656810 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-18 | criteria provided, single submitter | clinical testing | The p.V215A variant (also known as c.644T>C), located in coding exon 6 of the PMS2 gene, results from a T to C substitution at nucleotide position 644. The valine at codon 215 is replaced by alanine, an amino acid with 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 this alteration remains unclear. |