ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2113del (p.Val705fs) (rs63749811)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030250 SCV000107421 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Integrated Genetics/Laboratory Corporation of America RCV000030250 SCV000052917 pathogenic Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Ambry Genetics RCV000223638 SCV000278375 pathogenic Hereditary cancer-predisposing syndrome 2017-08-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000791368 SCV000548168 pathogenic Hereditary nonpolyposis colon cancer 2018-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val705Trpfs*5) 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 to segregate with Lynch syndrome-related cancers in several families (PMID: 8723682). In addition, this variant has been observed in unrelated individuals affected with Lynch syndrome (PMID: 18566915, 20052760, 8872463). ClinVar contains an entry for this variant (Variation ID: 1760). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000482957 SCV000568634 pathogenic not provided 2017-08-04 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH2 is denoted c.2113delG at the cDNA level and p.Val705TrpfsX5 (V705WfsX5) at the protein level. The normal sequence, with the base that is deleted in braces, is CATT[G]TGGA. The deletion causes a frameshift which changes a Valine to a Tryptophan at codon 705, and creates a premature stop codon at position 5 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.2113delG has been reported in families who meet Amsterdam criteria for Lynch syndrome and families suspicious for Lynch syndrome (Jeon 1996, Moslein 1996, Lin 1999, Domingo 2004, Hegde 2005, Nilbert 2009, Coolbaugh-Murphy 2010). Based on currently available evidence, we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482957 SCV000601455 pathogenic not provided 2017-06-16 criteria provided, single submitter clinical testing
OMIM RCV000001830 SCV000021986 pathogenic Lynch syndrome I 1996-01-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.