Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001067465 | SCV001232530 | uncertain significance | not provided | 2024-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 33 of the MSH3 protein (p.Ser33Gly). This variant is present in population databases (no rsID available, 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: 861045). 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 tolerated. 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 | RCV002379603 | SCV002694973 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-19 | criteria provided, single submitter | clinical testing | The p.S33G variant (also known as c.97A>G), located in coding exon 1 of the MSH3 gene, results from an A to G substitution at nucleotide position 97. The serine at codon 33 is replaced by glycine, an amino acid with similar 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. |
| St. |
RCV003230279 | SCV003928072 | uncertain significance | Familial adenomatous polyposis 4 | 2023-03-29 | criteria provided, single submitter | clinical testing | The MSH3 c.97A>G (p.Ser33Gly) missense change has a maximum subpopulation frequency of 0.017% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with MSH3-associated familial adenomatous polyposis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV003462603 | SCV004195163 | uncertain significance | Endometrial carcinoma | 2023-06-26 | criteria provided, single submitter | clinical testing |