Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234564 | SCV001407216 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with arginine at codon 791 of the PMS2 protein (p.Ser791Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 | RCV002447172 | SCV002735045 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-04 | criteria provided, single submitter | clinical testing | The p.S791R variant (also known as c.2373C>G), located in coding exon 14 of the PMS2 gene, results from a C to G substitution at nucleotide position 2373. The serine at codon 791 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |