ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1801C>T (p.Gln601Ter) (rs63750047)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491732 SCV000580481 pathogenic Hereditary cancer-predisposing syndrome 2017-06-30 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)
GeneDx RCV000428558 SCV000515989 pathogenic not provided 2017-07-28 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1801C>T at the cDNA level and p.Gln601Ter (Q601X) 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 observed in an individual with early onset colorectal cancer, whose tumor studies demonstrated microsatellite instability (Farrington 1998). Additionally, this variant has been reported in a family with Muir-Torre syndrome and is considered pathogenic (Kolodner 1994).
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076290 SCV000107311 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Invitae RCV000809096 SCV000949236 pathogenic Hereditary nonpolyposis colon cancer 2018-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln601*) 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 observed in an individual affected with colorectal cancer (PMID: 7585065). Also, it has been reported to segregate in a Lynch syndrome family (PMID: 7713503). This variant is also known as p.Q600Ter in the literature. ClinVar contains an entry for this variant (Variation ID: 1758). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001828 SCV000021984 pathogenic Muir-Torré syndrome 1994-12-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000428558 SCV000601441 pathogenic not provided 2016-01-27 criteria provided, single submitter clinical testing

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