Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002405905 | SCV002704243 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-07 | criteria provided, single submitter | clinical testing | The p.T558S variant (also known as c.1673C>G), located in coding exon 11 of the PMS2 gene, results from a C to G substitution at nucleotide position 1673. The threonine at codon 558 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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, |
RCV003493947 | SCV004243281 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004007348 | SCV004819923 | uncertain significance | Lynch syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with serine at codon 558 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 1/251268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |