ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.811_814del (p.Ser271fs) (rs587779185)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076726 SCV000107761 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000627723 SCV000257481 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-09-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser271Argfs*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 reported in individuals and families affected with Lynch syndrome-related cancers (PMID: 7585065, 9718327, 27601186, 15235034, 17312306). This variant is also known as 811del4 and 808_811delCTGT in the literature. ClinVar contains an entry for this variant (Variation ID: 91222). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000410668 SCV000488734 pathogenic Lynch syndrome I 2016-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491865 SCV000580510 pathogenic Hereditary cancer-predisposing syndrome 2017-11-27 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Integrated Genetics/Laboratory Corporation of America RCV000076726 SCV000696284 pathogenic Lynch syndrome 2017-08-17 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.811_814delTCTG (p.Ser271Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 121074 control chromosomes. Multiple publications have cited the variant in affected individuals and observed loss of MSH2 protein expression. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000069 SCV000885713 pathogenic not specified 2018-08-31 criteria provided, single submitter clinical testing The MSH2 c.811_814del; p.Ser271fs variant (also known as 808delGTCT) is reported in the medical literature in at least two individuals that fulfilled diagnostic criteria for HNPCC (Ewald 2007, Farrington 1998, Lagerstedt 2007, Liu 1995). The variant is described in the ClinVar database (Variation ID: 91222), in the dbSNP variant database (rs587779185), but is not listed in the general population-based databases (Exome Variant Server, Genome Aggregation Database). The variant deletes four nucleotides, creates a frameshift and is predicted to result in a truncated protein or mRNA subject to non-sense mediated decay. Considering available information, this variant is classified as pathogenic. References Ewald J et al. Immunohistochemical staining for mismatch repair proteins, and its relevance in the diagnosis of hereditary non-polyposis colorectal cancer. Br J Surg. 2007 Aug;94(8):1020-7. Farrington SM et al. Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. Am J Hum Genet. 1998 Sep;63(3):749-59. Lagerstedt Robinson K et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007 Feb 21;99(4):291-9. Liu B et al. Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med. 1995 Apr;1(4):348-52.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000757472 SCV000888234 pathogenic not provided 2017-09-11 criteria provided, single submitter clinical testing

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