Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000796361 | SCV000935871 | uncertain significance | not provided | 2024-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 683 of the MSH3 protein (p.Glu683Val). This variant is present in population databases (rs778485136, gnomAD 0.003%). 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: 642822). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 |
RCV000796361 | SCV002549462 | uncertain significance | not provided | 2024-08-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002422711 | SCV002726181 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | The p.E683V variant (also known as c.2048A>T), located in coding exon 14 of the MSH3 gene, results from an A to T substitution at nucleotide position 2048. The glutamic acid at codon 683 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004569541 | SCV005053619 | uncertain significance | Endometrial carcinoma | 2024-02-22 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000796361 | SCV005623804 | uncertain significance | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | The MSH3 c.2048A>T (p.Glu683Val) variant has not been reported in individuals with MSH3-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251136 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |