ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3699_3702del (p.Lys1233fs) (rs193922343)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128914 SCV000172781 pathogenic Hereditary cancer-predisposing syndrome 2017-12-15 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)
Color RCV000128914 SCV000903767 pathogenic Hereditary cancer-predisposing syndrome 2016-10-12 criteria provided, single submitter clinical testing
Counsyl RCV000576542 SCV000677728 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2015-06-03 criteria provided, single submitter clinical testing
GeneDx RCV000202074 SCV000279110 pathogenic not provided 2017-12-04 criteria provided, single submitter clinical testing This deletion of four nucleotides in MSH6 is denoted c.3699_3702delAGAA at the cDNA level and p.Lys1233AsnfsX6 (K1233NfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTAA[delAGAA]CTTG. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 1233, and creates a premature stop codon at position 6 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. MSH6 c.3699_3702delAGAA has been reported in association with Lynch syndrome (Bonadona 2011, Goldberg 2014, Raymond 2015, Yurgelun 2015, Ring 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000030271 SCV000052938 pathogenic Lynch syndrome 2015-04-03 no assertion criteria provided clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030271 SCV000108129 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000524183 SCV000551259 pathogenic Hereditary nonpolyposis colon cancer 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1233Asnfs*6) in the MSH6 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 affected with Lynch syndrome (PMID: 18389388, 21642682). This variant is also known as c.3697_3700delAAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 36593). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202074 SCV000257273 pathogenic not provided no assertion criteria provided research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202074 SCV000601584 pathogenic not provided 2016-07-14 criteria provided, single submitter clinical testing

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.