Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001038964 | SCV001202469 | uncertain significance | not provided | 2024-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 991 of the MSH3 protein (p.Tyr991Cys). This variant is present in population databases (rs766742870, gnomAD 0.007%). 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: 837592). 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. |
| Ambry Genetics | RCV002434445 | SCV002746186 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.Y991C variant (also known as c.2972A>G), located in coding exon 21 of the MSH3 gene, results from an A to G substitution at nucleotide position 2972. The tyrosine at codon 991 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001038964 | SCV004167964 | uncertain significance | not provided | 2023-11-01 | 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; This variant is associated with the following publications: (PMID: 28891274) |
| Baylor Genetics | RCV003461444 | SCV004197060 | uncertain significance | Endometrial carcinoma | 2023-09-29 | criteria provided, single submitter | clinical testing | |
| Genomic Medicine Center of Excellence, |
RCV003988859 | SCV004805519 | uncertain significance | Familial adenomatous polyposis 4 | 2024-03-25 | criteria provided, single submitter | research |