ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.349A>G (p.Met117Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002948694 SCV003278008 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-08-16 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 117 of the MLH3 protein (p.Met117Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Ambry Genetics RCV004068073 SCV003999117 uncertain significance not specified 2023-03-29 criteria provided, single submitter clinical testing The p.M117V variant (also known as c.349A>G), located in coding exon 1 of the MLH3 gene, results from an A to G substitution at nucleotide position 349. The methionine at codon 117 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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