ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.316C>G (p.Gln106Glu)

gnomAD frequency: 0.00010  dbSNP: rs149350323
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822585 SCV000963394 uncertain significance not provided 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 106 of the MSH3 protein (p.Gln106Glu). This variant is present in population databases (rs149350323, gnomAD 0.01%). 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: 664483). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamic acid 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 RCV001018944 SCV001180242 likely benign Hereditary cancer-predisposing syndrome 2019-05-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Sema4, Sema4 RCV001018944 SCV002536500 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-10 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153868 SCV003843034 uncertain significance Familial adenomatous polyposis 4 2023-02-09 criteria provided, single submitter clinical testing The MSH3 c.316C>G (p.Gln106Glu) missense change has a maximum subpopulation frequency of 0.014% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. This variant has been reported in individuals with colorectal cancer (PMID: 28944238). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
GeneDx RCV000822585 SCV003923873 uncertain significance not provided 2024-06-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Variant observed in individuals with colorectal cancer and/or polyps, and absent in controls (PMID: 28944238); This variant is associated with the following publications: (PMID: 28944238)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000822585 SCV005623830 uncertain significance not provided 2024-07-03 criteria provided, single submitter clinical testing The MSH3 c.316C>G (p.Gln106Glu) variant has been identified in the published literature in a reportedly healthy individual (PMID: 29641532 (2018)). This variant has also been identified in a cohort of individuals with colorectal cancer and reportedly healthy individuals (PMID: 28944238 (2017)). The frequency of this variant in the general population, 0.00024 (12/50792 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics RCV005047118 SCV005673161 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-06-14 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.