ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3347C>G (p.Ala1116Gly)

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
Labcorp Genetics (formerly Invitae), Labcorp RCV003870813 SCV004677096 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-11-04 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1116 of the MLH3 protein (p.Ala1116Gly). This variant is present in population databases (rs769952122, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. 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 glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV004828006 SCV005444165 uncertain significance not specified 2024-09-01 criteria provided, single submitter clinical testing The p.A1116G variant (also known as c.3347C>G), located in coding exon 2 of the MLH3 gene, results from a C to G substitution at nucleotide position 3347. The alanine at codon 1116 is replaced by glycine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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.