ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1222dup (p.Tyr408fs) (rs63751142)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076069 SCV000107084 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing a premature termination codon
GeneDx RCV000479156 SCV000568627 pathogenic not provided 2016-12-22 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH2 is denoted c.1222dupT at the cDNA level and p.Tyr408LeufsX9 (Y408LfsX9) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is ACTC[dupT]ATCA. The duplication causes a frameshift which changes a Tyrosine to a Leucine at codon 408, and creates a premature stop codon at position 9 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. MSH2 c.1222dupT has been reported in association with Lynch syndrome (Casey 2005). We consider this variant to be pathogenic.
Ambry Genetics RCV000491975 SCV000580539 pathogenic Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076069 SCV000592493 pathogenic Lynch syndrome 2015-05-29 criteria provided, single submitter clinical testing
Invitae RCV000629830 SCV000750786 pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr408Leufs*9) 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 and families affected with Lynch syndrome or Lynch syndrome-related cancer (PMID: 12624141, 15713769, 15849733, 15955785, 15926618). This variant is also known as c.1223insT, c.1222_1223insT in the literature. ClinVar contains an entry for this variant (Variation ID: 90573). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000479156 SCV001334860 pathogenic not provided 2020-04-01 criteria provided, single submitter clinical testing

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