ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.2650G>A (p.Glu884Lys)

gnomAD frequency: 0.00030  dbSNP: rs61752723
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 RCV000795311 SCV000934766 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 884 of the MLH3 protein (p.Glu884Lys). This variant is present in population databases (rs61752723, gnomAD 0.009%). 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: 641949). 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 tolerated. 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 RCV004027520 SCV002739834 uncertain significance not specified 2023-03-21 criteria provided, single submitter clinical testing The p.E884K variant (also known as c.2650G>A), located in coding exon 1 of the MLH3 gene, results from a G to A substitution at nucleotide position 2650. The glutamic acid at codon 884 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration 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.