ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.-8G>T (rs761672073)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000773113 SCV000906598 likely benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
GeneDx RCV000759815 SCV000567995 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.-8G>T, and describes a nucleotide substitution 8 base pairs upstream of the MLH1 ATG translational start site in the 5' untranslated region (UTR). Although this variant does not appear to affect the start codon or the Kozak translational consensus sequence, 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 translational silencing (Hitchins and Ward 2009, Ward 2013). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The guanine (G) nucleotide that is altered is not conserved across species. At this time, we consider MLH1 c.-8G>T to be a variant of uncertain significance
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759815 SCV000889409 uncertain significance not provided 2018-05-23 criteria provided, single submitter clinical testing

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