Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689403 | SCV000817051 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-22 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 568903). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 443 of the PMS2 protein (p.Arg443Gly). |
Ambry Genetics | RCV002386181 | SCV002689095 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.R443G variant (also known as c.1327A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1327. The arginine at codon 443 is replaced by glycine, an amino acid with dissimilar 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. |
Color Diagnostics, |
RCV002386181 | SCV004359618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glycine at codon 443 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 1/251434 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. |