ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.41G>A (p.Arg14His)

gnomAD frequency: 0.00001  dbSNP: rs760072474
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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 RCV000655381 SCV000777311 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 14 of the MLH3 protein (p.Arg14His). This variant is present in population databases (rs760072474, gnomAD 0.003%). 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: 544268). 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268239 SCV002551460 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002268239 SCV002631504 uncertain significance not specified 2023-06-07 criteria provided, single submitter clinical testing The p.R14H variant (also known as c.41G>A), located in coding exon 1 of the MLH3 gene, results from a G to A substitution at nucleotide position 41. The arginine at codon 14 is replaced by histidine, 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.

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