Titin mutations and muscle disease

Dalma Kellermayer, John E. Smith, Henk Granzier

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


The introduction of next-generation sequencing technology has revealed that mutations in the gene that encodes titin (TTN) are linked to multiple skeletal and cardiac myopathies. The most prominent of these myopathies is dilated cardiomyopathy (DCM). Over 60 genes are linked to the etiology of DCM, but by far, the leading cause of DCM is mutations in TTN with truncating variants in TTN (TTNtvs) associated with familial DCM in 20% of the cases. Titin is a large (3-4 MDa) and abundant protein that forms the third myofilament type of striated muscle where it spans half the sarcomere, from the Z-disk to the M-line. The underlying mechanisms by which titin mutations induce disease are poorly understood and targeted therapies are not available. Here, we review what is known about TTN mutations in muscle disease, with a major focus on DCM. We highlight that exon skipping might provide a possible therapeutic avenue to address diseases that arise from TTNtvs.

Original languageEnglish (US)
Pages (from-to)673-682
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Issue number5
StatePublished - May 2019


  • Dilated cardiomyopathy
  • Exon skipping
  • Mutations
  • TTNtv
  • Titin

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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