ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1910A>G (p.Glu637Gly)

dbSNP: rs376488647
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795209 SCV000934655 uncertain significance not provided 2024-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 637 of the MSH3 protein (p.Glu637Gly). This variant is present in population databases (rs376488647, 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: 641869). 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 RCV002406742 SCV002720556 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-30 criteria provided, single submitter clinical testing The p.E637G variant (also known as c.1910A>G), located in coding exon 14 of the MSH3 gene, results from an A to G substitution at nucleotide position 1910. The glutamic acid at codon 637 is replaced by glycine, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV000795209 SCV003921595 uncertain significance not provided 2023-03-15 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
Baylor Genetics RCV003461083 SCV004197097 uncertain significance Endometrial carcinoma 2023-09-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000795209 SCV004221055 uncertain significance not provided 2024-07-30 criteria provided, single submitter clinical testing The MSH3 c.1910A>G (p.Glu637Gly) variant has not been reported in individuals with MSH3-related conditions in the published literature. The frequency of this variant in the general population, 0.000035 (4/113460 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 predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV005036142 SCV005666194 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-01-17 criteria provided, single submitter clinical testing

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