ArticleThe Journal of clinical investigation2024
Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Review
- Variant Site-Specific Natural History of Titin-Induced Cardiomyopathy: An International Multicenter Registry.Circulation. Genomic and precision medicine · 2026Article
- Genotype-phenotype correlations in patients with pathogenic/likely pathogenic titin variants from the Swiss Arrhythmogenic Cardiomyopathy Registry.Open heart · 2026Observational
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Location-Dependent Differences in Cardiac and Skeletal Muscle Dysfunction Associated With Truncating Titin (Circulation research · 2026Article
- Titin Cardiomyopathy, Emerging Evidence: More Than A Big Heart.Current cardiology reports · 2025Review
- HDAC5 Inhibition as a Therapeutic Strategy for Titin Deficiency-Induced Cardiac Remodeling: Insights from Human iPSC Models.Medicines (Basel, Switzerland) · 2025Article
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- Formation of an Amyloid-like Structure During In Vitro Interaction of Titin and Myosin-Binding Protein C.International journal of molecular sciences · 2025Article
- Marfan syndrome cardiomyocytes show excess of titin isoform N2BA and extended sarcomeric M-band.The Journal of general physiology · 2025Article
- TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients.Orphanet journal of rare diseases · 2025Article
- Regulation of TTN as a mechanism of and treatment for heart failure.The Journal of clinical investigation · 2025Article
- An overview of insights and updates on TTN mutations in cardiomyopathies.Frontiers in pharmacology · 2025Review
- Titin truncating variants, cardiovascular risk factors and the risk of atrial fibrillation and heart failure.Nature cardiovascular research · 2024Article
- TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance.The Journal of clinical investigation · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here, we studied 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis, and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene sequence predictions were detected in the majority of the TTNtv+ samples. Full-length titin was reduced in TTNtv+ compared with TTNtv- samples. Proteomics analysis of washed myofibrils and stimulated emission depletion (STED) super-resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin was structurally integrated into the sarcomere. Sarcomere length-dependent anti-titin epitope position, shape, and intensity analyses pointed at possible structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres, which probably contribute, possibly via faulty mechanosensor function, to the development of manifest DCM.
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