ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.686_687del (p.Lys229fs) (rs63749897)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115539 SCV000149448 pathogenic not provided 2014-01-10 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.686_687delAA at the cDNA level and p.Lys229SerfsX2 (K229SfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAAAAA[delAA]GCTG. The deletion causes a frameshift, which changes a Lysine to a Serine at codon 229, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not been previously reported to our knowledge, it is considered pathogenic.
Invitae RCV000801666 SCV000941454 pathogenic Hereditary nonpolyposis colon cancer 2019-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys229Serfs*2) 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 with colon cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 127650). 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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