Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000805342 | SCV000945295 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 533 of the MSH3 protein (p.Glu533Lys). This variant is not present in population databases (gnomAD no frequency). 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: 650232). 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. |
Gene |
RCV000805342 | SCV002588264 | uncertain significance | not provided | 2022-04-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003362957 | SCV004056874 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-01 | criteria provided, single submitter | clinical testing | The p.E533K variant (also known as c.1597G>A), located in coding exon 11 of the MSH3 gene, results from a G to A substitution at nucleotide position 1597. The glutamic acid at codon 533 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Fulgent Genetics, |
RCV005036175 | SCV005666186 | uncertain significance | Endometrial carcinoma; Familial adenomatous polyposis 4 | 2024-01-31 | criteria provided, single submitter | clinical testing |