ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2502_2508del (p.Asn835fs) (rs63751447)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076489 SCV000107518 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000163822 SCV000214407 pathogenic Hereditary cancer-predisposing syndrome 2018-05-21 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000202117 SCV000568055 pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing This deletion of seven nucleotides in MSH2 is denoted c.2502_2508delTAATTTC at the cDNA level and p.Asn835LeufsX4 (N835LfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTGC[delTAATTTC]CCTA. The deletion causes a frameshift, which changes an Asparagine to a Leucine at codon 835, and creates a premature stop codon at position 4 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.2502_2508delTAATTTC has been observed in multiple individuals with Lynch syndrome associated cancers (Scott 2001, Sjursen 2016). Based on currently available information, we consider MSH2 c.2502_2508delTAATTTC to be pathogenic.
Invitae RCV001051236 SCV001215380 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn835Leufs*4) 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 individual(s) with clinical features of Lynch syndrome (PMID: 11112663, 12200596). ClinVar contains an entry for this variant (Variation ID: 90987). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202117 SCV000257179 likely pathogenic not provided no assertion criteria provided research

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