ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.2141G>A (p.Trp714Ter) (rs63751022)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075553 SCV000106549 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon with functional domain
Ambry Genetics RCV000165669 SCV000216407 pathogenic Hereditary cancer-predisposing syndrome 2017-05-30 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)
Integrated Genetics/Laboratory Corporation of America RCV000075553 SCV000696149 pathogenic Lynch syndrome 2016-07-06 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.2141G>A (p.Trp714X) variant results in a premature termination codon, predicted to cause a truncation of C-terminal domain, a known mechanisms for disease. The functional studies demonstrated that hMLH1-hMRE11 interaction was dramatically decreased by p.Trp714X, and truncated protein lacks MMR activity. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.2179_2182delCACA/p.His727fsX55). This variant has been reported in numerous Lynch Syndrome patients and is absent in 121240 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Pathway Genomics RCV000144606 SCV000189933 pathogenic Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing

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