Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001070980 | SCV001236260 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-08-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PMS2-related conditions. The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 811 of the PMS2 protein (p.Ala811Val). ClinVar contains an entry for this variant (Variation ID: 863908). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function. |
| Ambry Genetics | RCV002445367 | SCV002735303 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-03 | criteria provided, single submitter | clinical testing | The p.A811V variant (also known as c.2432C>T), located in coding exon 14 of the PMS2 gene, results from a C to T substitution at nucleotide position 2432. The alanine at codon 811 is replaced by valine, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Center for Genomic Medicine, |
RCV003493795 | SCV004243276 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |