ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2269_2270del (p.Thr757fs) (rs876661025)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216101 SCV000279250 pathogenic not provided 2016-01-21 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in MSH6 is denoted c.2269_2270delAC at the cDNA level and p.Thr757ProfsX6 (T757PfsX6) at the protein level. The normal sequence, with the bases that are deleted in brace, is AGGA[AC]CCTA. The deletion causes a frameshift, which changes a Threonine to a Proline at codon 757, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Invitae RCV000688578 SCV000816197 pathogenic Hereditary nonpolyposis colon cancer 2018-06-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr757Profs*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 not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 234448). 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.