ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.-22C>T (rs771060933)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000391041 SCV000443323 uncertain significance Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000480083 SCV000569091 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.-22C>T, and describes a nucleotide substitution 22 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 at a significant frequency in large population cohorts (Lek 2016). The variant occurs at a base that is not conserved. At this time, we consider MLH1 c.-22C>T to be a variant of uncertain significance.

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