ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.6C>G (p.Ile2Met)

gnomAD frequency: 0.00001  dbSNP: rs776416749
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001058280 SCV001222838 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2023-03-21 criteria provided, single submitter clinical testing 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. 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. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2 of the MLH3 protein (p.Ile2Met). This variant is present in population databases (rs776416749, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 853472).
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321792 SCV004027541 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV003321792 SCV004091267 uncertain significance not specified 2023-07-11 criteria provided, single submitter clinical testing The p.I2M variant (also known as c.6C>G), located in coding exon 1 of the MLH3 gene, results from a C to G substitution at nucleotide position 6. The isoleucine at codon 2 is replaced by methionine, an amino acid with highly 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. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Fulgent Genetics, Fulgent Genetics RCV005005016 SCV005633335 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-01-10 criteria provided, single submitter clinical testing

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