Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000475453 | SCV000552006 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 461 of the PMS2 protein (p.Ala461Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 411053). 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. |
Ambry Genetics | RCV000564795 | SCV000670797 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | The p.A461V variant (also known as c.1382C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1382. The alanine at codon 461 is replaced by valine, an amino acid with 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. |
Color Diagnostics, |
RCV000564795 | SCV001733654 | likely benign | Hereditary cancer-predisposing syndrome | 2017-01-23 | criteria provided, single submitter | clinical testing |