ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.2091C>T (p.Leu697=) (rs536488280)

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
GeneDx RCV000428650 SCV000531724 likely benign not specified 2016-09-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000526146 SCV000625125 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000566789 SCV000669558 likely benign Hereditary cancer-predisposing syndrome 2016-02-04 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Color RCV000566789 SCV000684799 likely benign Hereditary cancer-predisposing syndrome 2015-07-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000428650 SCV000917639 likely benign not specified 2018-02-07 criteria provided, single submitter clinical testing Variant summary: MLH1 c.2091C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0001 in 120336 control chromosomes, predominantly observed within the South Asian subpopulation at a frequency of 0.00073 in the ExAC database. This frequency is somewhat higher than expected for a pathogenic variant in MLH1 causing Lynch Syndrome (0.00073 vs 0.00071), suggesting that it is a benign polymorphism predominantly observed in the South Asian subpopulation. To our knowledge, no occurrence of c.2091C>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000428650 SCV000691866 likely benign not specified no assertion criteria provided 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.