Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000571183 | SCV000663559 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-31 | criteria provided, single submitter | clinical testing | The p.G495R variant (also known as c.1483G>C), located in coding exon 11 of the PMS2 gene, results from a G to C substitution at nucleotide position 1483. The glycine at codon 495 is replaced by arginine, an amino acid with dissimilar 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. |
Invitae | RCV001220537 | SCV001392532 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-06-18 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 495 of the PMS2 protein (p.Gly495Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. 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 PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 480370). 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. |