Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000807326 | SCV000947373 | uncertain significance | not provided | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 49 of the MSH3 protein (p.Pro49Ser). This variant is present in population databases (rs775307118, gnomAD 0.006%). 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: 651887). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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 | RCV002390616 | SCV002696968 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-28 | criteria provided, single submitter | clinical testing | The p.P49S variant (also known as c.145C>T), located in coding exon 1 of the MSH3 gene, results from a C to T substitution at nucleotide position 145. The proline at codon 49 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Prevention |
RCV003424349 | SCV004118234 | uncertain significance | MSH3-related disorder | 2023-03-01 | criteria provided, single submitter | clinical testing | The MSH3 c.145C>T variant is predicted to result in the amino acid substitution p.Pro49Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-79950691-C-T). It is interpreted as uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/651887/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003461169 | SCV004197017 | uncertain significance | Endometrial carcinoma | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000807326 | SCV004221039 | uncertain significance | not provided | 2022-09-10 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000055 (6/108140 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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. |
| Department of Pathology and Laboratory Medicine, |
RCV005392420 | SCV006057928 | uncertain significance | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-12-09 | criteria provided, single submitter | clinical testing |