ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.72669del (p.Asp24224fs) (rs727504531)

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
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155681 SCV000205391 likely pathogenic Primary dilated cardiomyopathy 2015-03-13 criteria provided, single submitter clinical testing The p.Asp21656fs variant in TTN has been previously reported in 1 adolescent wit h DCM and segregated with disease in 3 affected family members (reported as c.67 746delT, p.Pro22582fs, Herman 2012). Data from large population studies is insuf ficient to assess its frequency in the general population. This variant is predi cted to cause a frameshift, which alters the protein?s amino acid sequence begin ning at position 21656 and leads to a premature termination codon 8 amino acids downstream. This alteration is then predicted to lead to a truncated or absent p rotein. Frameshift and other truncating variants in TTN are strongly associated with DCM, particularly if they are located in the exons encoding for the A-band region of the protein (Herman 2012, Pugh 2014), where this variant is located. I n summary, although additional studies are required to fully establish its clini cal significance, the p.Asp21656fs variant is likely pathogenic.
Invitae RCV000461414 SCV000542626 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-03-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 24224 (p.Asp24224Ilefs*8) of the TTN gene. It is expected to result in an absent or disrupted protein product. This variant is found in the A-band of this gene. Truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy (PMID: 25589632). This particular variant has been reported to segregate with dilated cardiomyopathy in one affected family (PMID: 22335739). This variant is also known as c.67745delT, p.Pro22582fs in the literature. Experimental studies have shown that this change leads to a deficit in force generation and impaired responses to mechanical and beta-adrenergic stress (PMID: 26315439). For these reasons, this variant has been classified as Pathogenic.
University of Washington Center for Mendelian Genomics, University of Washington RCV000155681 SCV001434756 uncertain significance Primary dilated cardiomyopathy no assertion criteria provided research

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.