ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2028_2029del (p.Lys676_Ser677insTer) (rs1064794055)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480920 SCV000567686 pathogenic not provided 2017-04-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH6 c.2028_2029delAA at the cDNA level and p.Ser677Ter (S677X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (AGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant was observed in at least one individual with colorectal cancer, whose tumor exhibited microsatellite instability and absence of MSH6 protein on immunohistochemistry (Graham 2015). This variant is considered pathogenic.
Invitae RCV000552884 SCV000624714 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-10-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser677*) 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 an individual affected with colorectal cancer (PMID: 26099011). ClinVar contains an entry for this variant (Variation ID: 419704). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001014127 SCV001174802 pathogenic Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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.