ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.-26G>A

dbSNP: rs1064795186
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480012 SCV000570751 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.-26G>A, and describes a nucleotide substitution 26 base pairs upstream of the MLH1 ATG translational start site in the 5' untranslated region (UTR). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Of note, constitutional epigenetic silencing of MLH1 has been suggested as an alternate mechanism responsible for Lynch syndrome and variants located within the 5' UTR have been shown to result in allele specific promoter methylation and subsequent transcriptional silencing (Hitchins 2009, Ward 2013). This variant was not observed in large population cohorts and occurs at a position that is not conserved (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). At this time, we consider MLH1 c.-26G>A to be a variant of uncertain significance.

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.