Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000694947 | SCV000823417 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 105 of the PMS2 protein (p.Gly105Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-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 and their clinical significance is uncertain. 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 | RCV002325392 | SCV002607668 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-16 | criteria provided, single submitter | clinical testing | The p.G105R variant (also known as c.313G>C), located in coding exon 4 of the PMS2 gene, results from a G to C substitution at nucleotide position 313. The glycine at codon 105 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |