ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1552C>T (p.Gln518Ter) (rs63750780)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657577 SCV000779314 pathogenic not provided 2015-03-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.1552C>T at the cDNA level and p.Gln518Ter (Q518X) 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 association with Lynch syndrome (Fidalgo 2000, Lage 2004) and is considered pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076192 SCV000107210 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Invitae RCV000701635 SCV000830446 pathogenic Hereditary nonpolyposis colon cancer 2018-02-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln518*) 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 a family affected with hereditary non-polyposis colorectal cancer (HNPCC) (PMID: 10713887). ClinVar contains an entry for this variant (Variation ID: 90696). 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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