ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1705_1706del (p.Glu569fs) (rs63750393)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030243 SCV000107273 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Integrated Genetics/Laboratory Corporation of America RCV000030243 SCV000052910 pathogenic Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
GeneDx RCV000115505 SCV000149414 pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.1705_1706delGA at the cDNA level and p.Glu569IlefsX2 (E569IfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is AACA[GA]ATAT. The deletion causes a frameshift, which changes a Glutamic Acid to an Isoleucine at codon 569, and creates a premature stop codon at position 2 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.1705_1706delGA, also reported as c.1705delAG and c.1704_1705delAG, has been reported in several families with Lynch syndrome (Apessos 2005, Mangold 2005, Kurzawski 2006, Stulp 2008, Choi 2009, Walsh 2010, Bauer 2011, De Lellis 2013). We consider this variant to be pathogenic.
Counsyl RCV000409229 SCV000489543 pathogenic Lynch syndrome I 2016-10-21 criteria provided, single submitter clinical testing
Invitae RCV000627733 SCV000548247 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-08-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu569Ilefs*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 the literature in individuals and families with Lynch syndrome (PMID: 15713769, 15849733, 20587412, 19698169, 24278394, 11920650, 15655560). This variant has also been reported in individuals with breast cancer (PMID: 16311127, 20215533) and an individual with prostate cancer and a family history of colorectal, duodenal and prostate cancer (PMID: 20872076). This variant is also known as c.1704_1705delAG. ClinVar contains an entry for this variant (Variation ID: 36569). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491995 SCV000580390 pathogenic Hereditary cancer-predisposing syndrome 2019-02-14 criteria provided, single submitter clinical testing Other strong data supporting pathogenic classification;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
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030243 SCV000592517 pathogenic Lynch syndrome criteria provided, single submitter clinical testing
Color RCV000491995 SCV000690016 pathogenic Hereditary cancer-predisposing syndrome 2020-05-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000115505 SCV000889424 pathogenic not provided 2018-01-31 criteria provided, single submitter clinical testing

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