Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000703519 | SCV000832422 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2025-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 833 of the PMS2 protein (p.His833Tyr). 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 variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580079). 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. |
| Gene |
RCV001766547 | SCV002008179 | uncertain significance | not provided | 2024-08-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Fukui2011[Chapter]) |
| Ambry Genetics | RCV002424699 | SCV002741070 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-29 | criteria provided, single submitter | clinical testing | The p.H833Y variant (also known as c.2497C>T), located in coding exon 15 of the PMS2 gene, results from a C to T substitution at nucleotide position 2497. The histidine at codon 833 is replaced by tyrosine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003460980 | SCV004205356 | uncertain significance | Lynch syndrome 4 | 2024-03-15 | criteria provided, single submitter | clinical testing |