ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.3382A>G (p.Met1128Val)

dbSNP: rs1221498955
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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 RCV000821999 SCV000962777 uncertain significance not provided 2024-11-12 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1128 of the MSH3 protein (p.Met1128Val). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 664002). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002245692 SCV002512399 uncertain significance Familial adenomatous polyposis 4 2021-10-14 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderate, BP4 supporting
Sema4, Sema4 RCV002257990 SCV002536520 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-15 criteria provided, single submitter curation
Ambry Genetics RCV002257990 SCV002616125 likely benign Hereditary cancer-predisposing syndrome 2024-08-09 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.
Fulgent Genetics, Fulgent Genetics RCV005047116 SCV005666222 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-02-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004751742 SCV005348490 uncertain significance MSH3-related disorder 2024-06-08 no assertion criteria provided clinical testing The MSH3 c.3382A>G variant is predicted to result in the amino acid substitution p.Met1128Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance by multiple submitters in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/664002/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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