ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3455G>A (p.Arg1152His)

gnomAD frequency: 0.00006  dbSNP: rs374041909
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655385 SCV000777315 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-12-05 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 1152 of the MLH3 protein (p.Arg1152His). This variant is present in population databases (rs374041909, 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: 544272). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237980 SCV002011210 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268240 SCV002551418 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002268240 SCV002618504 uncertain significance not specified 2023-03-06 criteria provided, single submitter clinical testing The p.R1152H variant (also known as c.3455G>A), located in coding exon 3 of the MLH3 gene, results from a G to A substitution at nucleotide position 3455. The arginine at codon 1152 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Fulgent Genetics, Fulgent Genetics RCV005010635 SCV005635762 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-05-13 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003403508 SCV004120064 uncertain significance MLH3-related disorder 2024-08-05 no assertion criteria provided clinical testing The MLH3 c.3455G>A variant is predicted to result in the amino acid substitution p.Arg1152His. This variant has been reported in an individual with malignant mesothelioma (Table 2. Cheung et al. 2021. PubMed ID: 34008015). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD and is interpreted as a variant of uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/544272/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.