ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1216C>T (p.Arg406Ter) (rs63751108)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030238 SCV000107079 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing a premature termination codon
Integrated Genetics/Laboratory Corporation of America RCV000030238 SCV000052905 pathogenic Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Ambry Genetics RCV000162489 SCV000212867 pathogenic Hereditary cancer-predisposing syndrome 2019-01-25 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000202291 SCV000292622 pathogenic not provided 2019-01-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.1216C>T at the cDNA level and p.Arg406Ter (R406X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple individuals with a personal and/or family history of Lynch-associated cancers, including those with absent MSH2 protein on tumor immunohistochemistry (Leach 1993, Kuismanen 2000, Kurzawski 2002, Casey 2005, Lagerstedt Robinson 2007, Grindedal 2009, Pastrello 2011, De Lellis 2013, Bashyam 2014, Ponti 2016, Vargas-Parra 2017). We, therefore, consider this variant to be pathogenic.
Invitae RCV000524334 SCV000548281 pathogenic Hereditary nonpolyposis colon cancer 2019-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 406 (p.Arg406*) of the MSH2 gene. It is expected to result in an absent or disrupted protein product. The variant is not present in population databases (ExAC no frequency). This variant has been reported in many families and individuals affected with Lynch syndrome (PMID: 8261515, 15713769, 20223024, 20591884, 24710284). ClinVar contains an entry for this variant (Variation ID: 1755). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030238 SCV000592492 pathogenic Lynch syndrome 2016-06-20 criteria provided, single submitter clinical testing
Counsyl RCV000001825 SCV000677733 pathogenic Lynch syndrome I 2017-05-12 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000001825 SCV000745638 pathogenic Lynch syndrome I 2017-08-10 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677885 SCV000804046 pathogenic Carcinoma of colon 2017-05-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202291 SCV000888199 pathogenic not provided 2015-11-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763491 SCV000894277 pathogenic Lynch syndrome I; Turcot syndrome; Muir-Torré syndrome 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000162489 SCV001345237 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
OMIM RCV000001825 SCV000021981 pathogenic Lynch syndrome I 1993-12-17 no assertion criteria provided literature only
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202291 SCV000257126 pathogenic not provided no assertion criteria provided research

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