SynthesisJournal of molecular and cellular cardiology2020
Meta-analysis of cardiomyopathy-associated variants in troponin genes identifies loci and intragenic hot spots that are associated with worse clinical outcomes.
Synthesis in Journal of molecular and cellular cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Homozygous TNNC1-A8V Causes Impaired Diastolic Function and Restrictive Cardiomyopathy in Children and Mice.Circulation. Genomic and precision medicine · 2026Article
- Hypertrophic cardiomyopathy-linked Tnnc1 variants are associated with distinct myopathic changes in slow skeletal muscle of mice.Journal of muscle research and cell motility · 2026Article
- Single cell transcriptomic landscape of adult and pediatric non-ischemic cardiomyopathy.Journal of molecular and cellular cardiology · 2026Review
- Article
- Cardiomyocyte Nuclear Pleomorphism in a Mouse Model of Inherited Hypertrophic Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Cardiac Troponin C E135A Variant Impairs Myofilament Response to PKA Phosphorylation and Is Associated With Autosomal Dominant Dilated Cardiomyopathy With Diastolic Dysfunction.Circulation. Genomic and precision medicine · 2025Article
- The role of the troponin T interactions with actin in regulation of cardiac thin filament revealed by the troponin T pathogenic variant Ile79Asn.Journal of molecular and cellular cardiology · 2025Article
- Frustration in physiology and molecular medicine.Molecular aspects of medicine · 2025Review
- Exploring the c.406 C > T variant in TNNI3 gene: pathogenic insights into restrictive cardiomyopathy.BMC medical genomics · 2025Article
- Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases.Animal cells and systems · 2025Review
- Integrating of Radiomics and Single-cell Transcriptomics Uncovers the Crucial Role of γδ T Cells in Lung Adenocarcinoma.Journal of Cancer · 2025Article
- Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.Biomedicines · 2024Review
- Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.Biomedicines · 2024Review
- Activated fibroblasts drive cellular interactions in end-stage pediatric hypertrophic cardiomyopathy.bioRxiv : the preprint server for biology · 2024Article
- In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused byFrontiers in physiology · 2024Article
- Nucleus Mechanosensing in Cardiomyocytes.International journal of molecular sciences · 2023Review
- Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C.International journal of molecular sciences · 2023Review
- Cardiac troponin T N-domain variant destabilizes the actin interface resulting in disturbed myofilament function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Comprehensive review on gene mutations contributing to dilated cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- The effect of MgThe FEBS journal · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
introductionTroponin (TNN)-encoded cardiac troponins (Tn) are critical for sensing calcium and triggering myofilament contraction. TNN variants are associated with development of cardiomyopathy; however, recent advances in genetic analysis have identified rare population variants. It is unclear how certain variants are associated with disease while others are tolerated.
objectiveTo compare probands with TNNT2, TNNI3, and TNNC1 variants and utilize high-resolution variant comparison mapping of pathologic and rare population variants to identify loci associated with disease pathogenesis.
methodsCardiomyopathy-associated TNN variants were identified in the literature and topology mapping conducted. Clinical features were compiled and compared. Rare population variants were obtained from the gnomAD database. Signal-to-noise (S:N) normalized pathologic variant frequency against population variant frequency. Abstract review of clinical phenotypes was applied to "significant" hot spots.
resultsProbands were compiled (N = 70 studies, 224 probands) as were rare variants (N = 125,748 exomes; 15,708 genomes, MAF <0.001). TNNC1-positive probands demonstrated the youngest age of presentation (20.0 years; P = .016 vs TNNT2; P = .004 vs TNNI3) and the highest death, transplant, or ventricular fibrillation events (P = .093 vs TNNT2; P = .024 vs TNNI3; Kaplan Meir: P = .025). S:N analysis yielded hot spots of diagnostic significance within the tropomyosin-binding domains, α-helix 1, and the N-Terminus in TNNT2 with increased sudden cardiac death and ventricular fibrillation (P = .004). The inhibitory region and C-terminal region in TNNI3 exhibited increased restrictive cardiomyopathy (P =.008). HCM and RCM models tended to have increased calcium sensitivity and DCM decreased sensitivity (P < .001). DCM and HCM studies typically showed no differences in Hill coefficient which was decreased in RCM models (P < .001). CM models typically demonstrated no changes to F
conclusionTNNC1-positive probands had younger ages of diagnosis and poorer clinical outcomes. Mapping of TNN variants identified locations in TNNT2 and TNNI3 associated with heightened pathogenicity, RCM diagnosis, and increased risk of sudden death.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.