ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.4175A>G (p.Gln1392Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004051834 SCV002630509 uncertain significance not specified 2022-10-09 criteria provided, single submitter clinical testing The p.Q1392R variant (also known as c.4175A>G), located in coding exon 11 of the MLH3 gene, results from an A to G substitution at nucleotide position 4175. The glutamine at codon 1392 is replaced by arginine, an amino acid with highly similar 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 RCV003614118 SCV004531844 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1392 of the MLH3 protein (p.Gln1392Arg). This variant is present in population databases (rs761452132, gnomAD 0.004%). 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: 1738444). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.