ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2779dup (p.Ile927fs) (rs587782277)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131134 SCV000186066 pathogenic Hereditary cancer-predisposing syndrome 2013-01-22 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000218611 SCV000279367 pathogenic not provided 2017-01-10 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH6 is denoted c.2779dupA at the cDNA level and p.Ile927AsnfsX8 (I927NfsX8) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACTT[A]TTAC. The duplication causes a frameshift, which changes an Isoleucine to an Asparagine at codon 927, and creates a premature stop codon at position 8 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.2779dupA has been identified in an individual undergoing hereditary cancer panel testing (LaDuca 2014). We consider this variant to be pathogenic.
Color RCV000131134 SCV000685324 pathogenic Hereditary cancer-predisposing syndrome 2020-03-27 criteria provided, single submitter clinical testing
Invitae RCV001237131 SCV001409882 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile927Asnfs*8) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs763978082, ExAC 0.002%). This variant has been observed in individuals with clinical indications of hereditary cancer syndromes, such as Lynch syndrome (PMID: 24763289, 27601186). ClinVar contains an entry for this variant (Variation ID: 142168). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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.