Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481815 | SCV000572040 | uncertain significance | not provided | 2023-06-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22949387) |
| Labcorp Genetics |
RCV000694864 | SCV000823326 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 567 of the PMS2 protein (p.Gln567Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 422543). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. 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. |
| Mendelics | RCV000987823 | SCV001137288 | uncertain significance | Lynch syndrome 4 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002402413 | SCV002714146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-20 | criteria provided, single submitter | clinical testing | The p.Q567R variant (also known as c.1700A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1700. The glutamine at codon 567 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly 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. |
| Center for Genomic Medicine, |
RCV005230948 | SCV005873354 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |