ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1827del (p.His610fs) (rs587779112)

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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) RCV000076297 SCV000107318 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000491249 SCV000580540 pathogenic Hereditary cancer-predisposing syndrome 2018-06-21 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000531842 SCV000625320 pathogenic Hereditary nonpolyposis colon cancer 2019-11-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His610Thrfs*25) 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 an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 90796). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000076297 SCV000917695 likely pathogenic Lynch syndrome 2018-10-09 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1827delT (p.His610ThrfsX25) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Arg621X and p.Arg680X). The variant was absent in 246248 control chromosomes. To our knowledge, no occurrence of c.1827delT in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Color RCV000491249 SCV001357029 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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