ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2536C>T (p.Gln846Ter) (rs63750857)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076498 SCV000107527 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
GeneDx RCV000657648 SCV000779395 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2536C>T at the cDNA level and p.Gln846Ter (Q846X) 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 individuals with Lynch syndrome (Mangold 2005, De Lellis 2013) and is considered pathogenic.
Invitae RCV001207810 SCV001379177 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-07-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln846*) 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 individuals affected with hereditary nonpolyposis colorectal cancer (PMID: 15849733, 24278394). ClinVar contains an entry for this variant (Variation ID: 90996). 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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