Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000629966 | SCV000750922 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2020-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with arginine at codon 373 of the PMS2 protein (p.Ser373Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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). |
| Ambry Genetics | RCV002438640 | SCV002747091 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-08 | criteria provided, single submitter | clinical testing | The p.S373R variant (also known as c.1119T>A), located in coding exon 10 of the PMS2 gene, results from a T to A substitution at nucleotide position 1119. The serine at codon 373 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
| Baylor Genetics | RCV003459493 | SCV004205490 | uncertain significance | Lynch syndrome 4 | 2023-08-08 | criteria provided, single submitter | clinical testing |