Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000217760 | SCV000274495 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | The p.S529L variant (also known as c.1586C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1586. The serine at codon 529 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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. |
Invitae | RCV000471239 | SCV000551968 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 529 of the PMS2 protein (p.Ser529Leu). This variant is present in population databases (no rsID available, gnomAD 0.009%). 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: 230822). 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 not expected to disrupt PMS2 protein function. 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 |
RCV000486303 | SCV000565415 | uncertain significance | not provided | 2022-01-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29596542) |
Color Diagnostics, |
RCV000217760 | SCV000903483 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 529 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 3/250986 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. |