Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016528 | SCV001177490 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.Y921C variant (also known as c.2762A>G), located in coding exon 20 of the MSH3 gene, results from an A to G substitution at nucleotide position 2762. The tyrosine at codon 921 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |
| Labcorp Genetics |
RCV001061278 | SCV001226016 | uncertain significance | not provided | 2024-12-31 | 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 921 of the MSH3 protein (p.Tyr921Cys). This variant is present in population databases (rs190723980, gnomAD 0.02%). 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: 821775). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001061278 | SCV002047109 | uncertain significance | not provided | 2024-10-24 | criteria provided, single submitter | clinical testing | The MSH3 c.2762A>G (p.Tyr921Cys) variant has not been reported in individuals with MSH3-related conditions in the published literature. The frequency of this variant in the general population, 0.00016 (4/24974 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. |
| Gene |
RCV001061278 | SCV003837376 | uncertain significance | not provided | 2022-08-30 | criteria provided, single submitter | clinical testing | 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 | RCV003461355 | SCV004196950 | uncertain significance | Endometrial carcinoma | 2024-02-24 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005036289 | SCV005666213 | uncertain significance | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-02-23 | criteria provided, single submitter | clinical testing |