ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.1937C>G (p.Thr646Arg)

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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 RCV003118970 SCV003789548 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-10-07 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 646 of the MLH3 protein (p.Thr646Arg).
Ambry Genetics RCV004245941 SCV003858112 uncertain significance not specified 2023-02-23 criteria provided, single submitter clinical testing The p.T646R variant (also known as c.1937C>G), located in coding exon 1 of the MLH3 gene, results from a C to G substitution at nucleotide position 1937. The threonine at codon 646 is replaced by arginine, an amino acid with 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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