ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1943C>T (p.Pro648Leu) (rs63750610)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075433 SCV000106429 likely pathogenic Lynch syndrome I 2018-06-13 reviewed by expert panel curation Variant reclassification due to new tumour Likelihood Ratios: Multifactorial likelihood analysis posterior probability > 0.95 (0.989)
Ambry Genetics RCV000221413 SCV000278137 pathogenic Hereditary cancer-predisposing syndrome 2012-08-14 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s);Well-characterized mutation at same position;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000812087 SCV000952391 pathogenic Hereditary nonpolyposis colon cancer 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 648 of the MLH1 protein (p.Pro648Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Lynch syndrome (PMID: 16083711, 11726306, 21404117, Invitae). ClinVar contains an entry for this variant (Variation ID: 89953). This variant has been reported to affect MLH1 protein function (PMID:20533529, 21404117, 16083711, 17510385, 22753075). This variant disrupts the p.Pro648 amino acid residue in MLH1. Other variant(s) that disrupt this residue have been observed in individuals with MLH1-related conditions (PMID: 15139004, 21404117, 18307539, 16724012, 16083711), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Color RCV000221413 SCV001343104 likely pathogenic Hereditary cancer-predisposing syndrome 2019-10-02 criteria provided, single submitter clinical testing
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477957 SCV000536722 likely pathogenic Turcot syndrome; Muir-Torré syndrome; Lynch syndrome II 2016-02-22 no assertion criteria provided research

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.