Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000816827 | SCV000957353 | uncertain significance | not provided | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1122 of the MSH3 protein (p.Trp1122Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 659774). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Ambry Genetics | RCV002453859 | SCV002612940 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-06 | criteria provided, single submitter | clinical testing | The p.W1122R variant (also known as c.3364T>C), located in coding exon 24 of the MSH3 gene, results from a T to C substitution at nucleotide position 3364. The tryptophan at codon 1122 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Gene |
RCV000816827 | SCV003919386 | uncertain significance | not provided | 2022-10-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |
Baylor Genetics | RCV003461243 | SCV004197124 | uncertain significance | Endometrial carcinoma | 2023-08-27 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000816827 | SCV005623842 | uncertain significance | not provided | 2024-04-02 | criteria provided, single submitter | clinical testing | The MSH3 c.3364T>C (p.Trp1122Arg) variant has not been reported in individuals with MSH3-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31404 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant. |