ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.80494G>T (p.Glu26832Ter)

dbSNP: rs780512337
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000220480 SCV000271282 likely pathogenic Primary dilated cardiomyopathy 2016-01-11 criteria provided, single submitter clinical testing The p.Glu24264X variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This nonsense variant leads t o a premature termination codon at position 24264 which is predicted to lead to a truncated or absent protein. Nonsense and other truncating variants in TTN are strongly associated with DCM if they impact the exons encoding for the A-band ( Herman 2012, Pugh 2014) or are located in an exon that is highly expressed in th e heart (Roberts 2015). This variant is located the highly expressed exon 275 of the A-band. In summary, although additional studies are required to fully estab lish its clinical significance, the p.Glu24264X variant is likely pathogenic.
GeneDx RCV000480047 SCV000570090 likely pathogenic not provided 2016-04-22 criteria provided, single submitter clinical testing The E25191X variant in the TTN gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. E25191X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other truncating TTN variants have been reported in approximately 3% of control alleles (Herman et al., 2012). However, E25191X is located in the A-band region of titin, where the majority of truncating pathogenic variants associated with DCM have been reported (Herman et al., 2012). Furthermore, the E25191X variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E25191X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.

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.