ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.40C>T (p.Arg14Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004051328 SCV002630597 uncertain significance not specified 2023-09-01 criteria provided, single submitter clinical testing The p.R14C variant (also known as c.40C>T), located in coding exon 1 of the MLH3 gene, results from a C to T substitution at nucleotide position 40. The arginine at codon 14 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005096482 SCV005846960 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-06-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 14 of the MLH3 protein (p.Arg14Cys). 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. ClinVar contains an entry for this variant (Variation ID: 1737831). 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. 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.

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