ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.1343C>T (p.Pro448Leu)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004058744 SCV002693677 uncertain significance not specified 2024-03-09 criteria provided, single submitter clinical testing The p.P448L variant (also known as c.1343C>T), located in coding exon 1 of the MLH3 gene, results from a C to T substitution at nucleotide position 1343. The proline at codon 448 is replaced by leucine, an amino acid with similar properties. This alteration has been reported in an individual with a personal history of papillary thyroid cancer (Mio C et al. Endocrine, 2021 09;73:648-657). This amino acid position is not conserved however, leucine is a reference amino acid in several species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003614146 SCV004464604 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 448 of the MLH3 protein (p.Pro448Leu). This variant is present in population databases (rs773056264, gnomAD 0.03%). 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: 1770407). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine 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.
Fulgent Genetics, Fulgent Genetics RCV005008569 SCV005635803 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-05-07 criteria provided, single submitter clinical testing

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.