Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214488 | SCV000277978 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.I15M variant (also known as c.45C>G), located in coding exon 2 of the PMS2 gene, results from a C to G substitution at nucleotide position 45. The isoleucine at codon 15 is replaced by methionine, an amino acid with highly 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. |
| Labcorp Genetics |
RCV001854698 | SCV002159157 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-06-25 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 233577). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 15 of the PMS2 protein (p.Ile15Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477764 | SCV004219010 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000066 (1/152188 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |