ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.3384G>A (p.Met1128Ile)

gnomAD frequency: 0.00002  dbSNP: rs767305989
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001247183 SCV001420590 uncertain significance not provided 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1128 of the MSH3 protein (p.Met1128Ile). This variant is present in population databases (rs767305989, gnomAD 0.05%). 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: 971412). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The isoleucine 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 RCV002451608 SCV002614548 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-14 criteria provided, single submitter clinical testing The p.M1128I variant (also known as c.3384G>A), located in coding exon 24 of the MSH3 gene, results from a G to A substitution at nucleotide position 3384. The methionine at codon 1128 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005040096 SCV005666223 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-02-22 criteria provided, single submitter clinical testing

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