ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1297G>T (p.Glu433Ter) (rs63750443)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000565642 SCV000673819 pathogenic Hereditary cancer-predisposing syndrome 2017-02-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Counsyl RCV000662367 SCV000784757 likely pathogenic Lynch syndrome II 2017-09-11 criteria provided, single submitter clinical testing
GeneDx RCV000519454 SCV000620630 pathogenic not provided 2018-03-12 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.1297G>T at the cDNA level and p.Glu433Ter (E433X) at the proteinlevel. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon(GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is consideredpathogenic
Invitae RCV000700958 SCV000829737 pathogenic Hereditary nonpolyposis colon cancer 2018-02-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu433*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic.

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