ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2228C>A (p.Ser743Ter) (rs63751155)

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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) RCV000076434 SCV000107463 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
GeneDx RCV000236386 SCV000293509 pathogenic not provided 2018-06-08 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2228C>A at the cDNA level and p.Ser743Ter (S743X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported families with Lynch syndrome (Pino 2009, Bonadona 2011) and is considered pathogenic.
Invitae RCV001062167 SCV001226947 pathogenic Hereditary nonpolyposis colon cancer 2019-02-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser743*) 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 several individuals affected with Lynch syndrome (PMID: 14514376, 19324997, 21642682). ClinVar contains an entry for this variant (Variation ID: 90932). 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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