ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.892C>T (p.Gln298Ter) (rs63750934)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3DMed Clinical Laboratory Inc RCV000677887 SCV000804048 pathogenic Malignant tumor of sigmoid colon 2017-12-27 no assertion criteria provided clinical testing
Ambry Genetics RCV000490887 SCV000580442 pathogenic Hereditary cancer-predisposing syndrome 2017-02-13 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)
GeneDx RCV000478579 SCV000568624 pathogenic not provided 2017-09-11 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.892C>T at the cDNA level and p.Gln298Ter (Q298X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple families with Lynch syndrome-associated cancers (Wahlberg 1999, Buchanan 2014, Rosty 2014, Therkildsen 2015, Whitworth 2016, Lagerstedt-Robinson 2016). We consider this variant to be pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076744 SCV000107781 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000629714 SCV000750670 pathogenic Hereditary nonpolyposis colon cancer 2018-05-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln298*) in the MSH2 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 been reported in multiple families and individuals affected with Lynch syndrome-related cancers (PMID: 10495924, 25117503, 26659639, 24323032, 28790115, 25648859, 12658575). ClinVar contains an entry for this variant (Variation ID: 91239). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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