Affinage

TNNT2

Troponin T, cardiac muscle · UniProt P45379

Length
298 aa
Mass
35.9 kDa
Annotated
2026-06-10
56 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNNT2 encodes cardiac troponin T, a thin-filament protein that couples cytosolic Ca2+ to actomyosin contraction in cardiomyocytes, and whose missense variants produce divergent cardiomyopathies through opposite shifts in myofilament Ca2+ handling (PMID:20031601, PMID:33025817). In isogenic hiPSC-derived cardiomyocytes and reconstituted thin filaments, HCM-associated variants raise myofilament Ca2+ affinity and contraction, while DCM-associated variants lower Ca2+ sensitivity and contractile force, and both classes drive graded transcriptomic responses including MAPK targets and NPPB induction that scale with the functional change (PMID:33025817, PMID:20031601). At the biophysical level, individual HCM variants slow the Ca2+ off-rate and raise diastolic Ca2+ to cause relaxation impairment, beat-to-beat instability, and Ca2+/voltage alternans that link the protein to arrhythmogenesis (PMID:34977031, PMID:37159677), with downstream hypertrophic signaling through NFATc1 nuclear translocation and CaMKIIδ/phospholamban phosphorylation (PMID:35861968); variant-specific effects extend to allosteric repositioning of cTnI that impairs PKA-mediated relaxation control (PMID:37503299). Beyond the sarcomere, altered contractile transients from pathogenic variants remodel lamin A/C and nuclear stiffness, a change rescued by myosin modulators, establishing mechanotransmission from sarcomere to nucleus (PMID:41321620). TNNT2 is also subject to developmentally regulated alternative splicing that is controlled by DYRK1A-dependent phosphorylation of the splicing factor SRSF6, a pathway dysregulated in trisomic (Down syndrome) myocardium (PMID:35596909, PMID:31201803, PMID:8088824). A reported nuclear role for TNNT2 as an HDAC1 sponge and a physical interaction with EGFR in colorectal cancer fall outside the validated sarcomeric mechanism in the current corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Established the gene's chromosomal location and that cardiac troponin T is expressed as multiple developmentally regulated isoforms, setting up alternative splicing as a feature of TNNT2 biology.

    Evidence Somatic cell hybrid mapping and cDNA cloning/hybridization in fetal human heart

    PMID:8088824

    Open questions at the time
    • Functional consequences of individual isoforms not defined
    • Regulators of the splicing not identified at this stage
  2. 2004 Medium

    Linked a TNNT2 intronic polymorphism to altered splicing (exon 4 skipping) and to left ventricular hypertrophy, connecting splice regulation to a structural cardiac phenotype.

    Evidence In vitro splicing assay plus clinical association with LV mass

    PMID:14986170

    Open questions at the time
    • Association does not establish causation of hypertrophy
    • Mechanism connecting exon 4 skipping to LV mass unresolved
  3. 2009 High

    Defined the unifying biophysical mechanism for DCM-causing variants — decreased Ca2+ sensitivity of force development — across multiple mutations.

    Evidence Cardiac myocyte reconstitution with mutant troponin T and Ca2+-sensitivity of force assays

    PMID:20031601

    Open questions at the time
    • In vitro reconstitution does not capture intact-cell or in vivo remodeling
    • Downstream signaling consequences not addressed
  4. 2010 Medium

    Showed in vivo that a pathogenic variant produces intrinsic cardiomyocyte dysfunction and heart-failure gene induction, arguing the primary defect is cell-autonomous rather than developmental.

    Evidence Transgenic mouse expressing mutant human cTnT with echocardiography, histology, and gene expression

    PMID:20083571

    Open questions at the time
    • Single variant in transgenic (non-knock-in) context
    • Calcium-handling mechanism not directly measured
  5. 2020 High

    Resolved the bidirectional genotype-phenotype rule at scale: HCM variants increase, and DCM variants decrease, both contraction and Ca2+ affinity, with transcriptomic output scaling to sarcomere function.

    Evidence CRISPR-engineered isogenic hiPSC-CMs (51 variants), microtissue contraction, Ca2+ reporter, RNA-seq, NPPB reporter

    PMID:33025817

    Open questions at the time
    • Mechanism converting sarcomere change to MAPK/NPPB transcription not dissected
    • Long-term remodeling not captured in microtissue timeframe
  6. 2021 High

    Connected an HCM variant's biophysical signature (slowed Ca2+ off-rate, raised Ca2+ sensitivity) to a cellular arrhythmogenic phenotype, providing a mechanistic chain to arrhythmia risk.

    Evidence Reconstituted thin filaments with stopped-flow kinetics plus I79N+/- hiPSC-CMs with voltage/Ca2+ transient measurement

    PMID:34977031

    Open questions at the time
    • Arrhythmia demonstrated in cellular model, not whole heart
    • Single variant
  7. 2022 High

    Extended the mechanism downstream to hypertrophic signaling, showing a Ca2+-retaining variant activates NFATc1 and CaMKIIδ/phospholamban phosphorylation, with pharmacological Ca2+ desensitization rescuing relaxation.

    Evidence Isogenic hiPSC-CMs with Ca2+ imaging, NFATc1 translocation imaging, signaling western blots, EGCG rescue

    PMID:35861968

    Open questions at the time
    • Causal ordering of Ca2+ retention versus signaling activation not fully resolved
    • In vivo relevance of EGCG rescue untested here
  8. 2022 High

    Demonstrated that elevated Ca2+ sensitivity is phosphorylation-independent and dominant at low mutant fraction, clarifying how heterozygous variants exert outsized effects.

    Evidence Patient cardiomyocyte force measurements, troponin exchange titration, phosphatase/PKA treatment, isogenic hiPSC-CMs

    PMID:37159677

    Open questions at the time
    • Generalizability of the 14% threshold to other variants unknown
    • Atrial versus ventricular differences not addressed
  9. 2022 Medium

    Established genotype-specific atrial pathomechanisms, distinguishing a Ca2+-sensitizing arrhythmogenic variant from an energetic-cost variant lacking arrhythmic propensity.

    Evidence R92Q and E163R HCM mouse models with atrial trabecula functional assays and echocardiography

    PMID:35514357

    Open questions at the time
    • Two variants do not define the full genotypic spectrum of atrial risk
    • Molecular basis of energy-cost increase not detailed
  10. 2022 Medium

    Identified DYRK1A-SRSF6 phosphorylation as the regulatory pathway controlling the developmental fetal-to-adult TNNT2 splice transition.

    Evidence DYRK1A overexpression in iPSC-CMs with RT-PCR splice quantification and phospho-SRSF6 western blot

    PMID:35596909

    Open questions at the time
    • Direct SRSF6 binding to TNNT2 pre-mRNA not shown
    • Functional consequence of fetal isoform shift not measured
  11. 2019 Medium

    Provided disease-context validation of the splicing pathway, showing SRSF6 hyperphosphorylation and fetal TNNT2 isoform enrichment in trisomy 21 myocardium.

    Evidence Phospho-DYRK1A/SRSF6 western blotting and TNNT2 isoform RT-PCR in human trisomic myocardial tissue

    PMID:31201803

    Open questions at the time
    • Correlative tissue measurement, not causal manipulation
    • Functional cardiac consequence in Down syndrome not established
  12. 2019 Medium

    Revealed a non-myocardial requirement for TNNT2, showing outflow-tract smooth muscle expression is indispensable for normal cardiac mechanical dynamics.

    Evidence tnnt2a zebrafish mutants with tissue-specific promoter rescue, RNA-seq, and cardiac function imaging

    PMID:31796423

    Open questions at the time
    • Mammalian conservation of the OFT smooth muscle role not shown
    • Molecular function of TNNT2 in smooth muscle cells undefined
  13. 2021 Medium

    Identified XIN/XINB as a modifier that can partially rescue a DCM variant phenotype, pointing to candidate therapeutic targets downstream of sarcomere dysfunction.

    Evidence TNNT2-ΔK210 hESC-CMs and mice with AAV9 XINB overexpression, echocardiography, histology

    PMID:34222259

    Open questions at the time
    • Mechanism of XIN reduction by ΔK210 not defined
    • Rescue is partial; durability unknown
  14. 2023 Medium

    Provided a structural-allosteric explanation for diastolic dysfunction, showing a variant repositions cTnI to impair PKA phosphorylation of the relaxation-regulating site.

    Evidence Mouse models, ex vivo hemodynamics, stopped-flow kinetics, TR-FRET, MD simulation, phosphomimetic rescue (preprint)

    PMID:37503299

    Open questions at the time
    • Preprint, not peer-reviewed
    • Variant-specific rescue (R92L not Δ160E) limits generality
  15. 2024 Medium

    Proposed a non-canonical nuclear function for TNNT2 as an HDAC1 sponge whose disruption causes epigenetic dysregulation, expanding the mechanism beyond sarcomere mechanics.

    Evidence Knock-in mice, LVNC patient iPSC-CMs, structural modeling, nuclear TNNT2-HDAC1 co-IP, pharmacological rescue (preprint)

    Open questions at the time
    • Preprint with no PMID; novel nuclear claim awaits independent replication
    • Single Co-IP for the nuclear interaction
    • Reciprocal validation and stoichiometry of the sponge model not established
  16. 2025 Medium

    Established a causal sarcomere-to-nucleus mechanotransmission axis, linking variant-altered contractile transients to lamin A/C and nuclear stiffness changes reversible by myosin modulators.

    Evidence hiPSC-CMs with HCM/DCM TNNT2 variants, transcriptomics, nuclear stiffness measurement, Mavacamten/Omecamtiv Mecarbil rescue

    PMID:41321620

    Open questions at the time
    • Molecular link from contractility to lamin remodeling not detailed
    • In vivo nuclear mechanics not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether the reported non-sarcomeric roles of TNNT2 — nuclear HDAC1 sponging and EGFR-driven EMT in cancer — represent bona fide physiological functions and how they integrate with the established thin-filament regulatory role.
  • Nuclear and cancer functions rest on single-lab/preprint or Low-confidence evidence
  • No reciprocal or independent validation of non-sarcomeric interactions
  • Physiological stoichiometry and context unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005634 nucleus 1
Pathway
R-HSA-397014 Muscle contraction 4 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3
Partners
EGFRHDAC1TNNC1TNNI3TPM1XIRP2
Complex memberships
cardiac thin filamentcardiac troponin complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Four novel TNNT2 missense mutations (Arg134Gly, Arg151Cys, Arg159Gln, Arg205Trp) and one previously reported (Glu244Asp) were functionally characterized in reconstituted cardiac myocytes; all caused decreased Ca2+ sensitivity of force development, a hallmark mechanism of dilated cardiomyopathy. Cardiac myocyte reconstitution with mutant troponin T proteins; Ca2+-sensitivity of force development assay Circulation. Cardiovascular genetics High 20031601
1994 The TNNT2 gene was mapped to chromosome 1q (1cen-qter) by somatic cell hybrid analysis, and multiple cardiac troponin T mRNA isoforms were demonstrated in fetal human heart resulting from alternative splicing in the 5' coding region. Somatic cell hybrid analysis; cDNA cloning and hybridization; genomic Southern blotting Genomics High 8088824
2004 A 5-bp insertion/deletion polymorphism in intron 3 of TNNT2 affects splicing: the deletion allele causes skipping of exon 4 during splicing, altering the mRNA expression pattern, and was associated with greater left ventricular hypertrophy. In vitro expression study; splicing analysis; association study with LV mass measurements Journal of human genetics Medium 14986170
2010 A novel TNNT2 missense mutation pE96K causes impaired left ventricular function and induction of heart failure marker genes in transgenic mice expressing the mutant human cTNT, without producing a left ventricular non-compaction phenotype, indicating intrinsic cardiomyocyte dysfunction as the primary pathological mechanism. Transgenic mouse model; echocardiography; histology; gene expression analysis Cardiovascular research Medium 20083571
2020 HCM-associated TNNT2 variants increased cardiac microtissue contraction and myofilament calcium affinity, whereas DCM-associated TNNT2 variants decreased contraction and calcium affinity; both disease classes induced graded transcriptomic changes including MAPK signaling targets and NPPB, which correlated directly with sarcomere functional changes. CRISPR/Cas9-engineered hiPSC-derived cardiomyocytes; cardiac microtissue contraction assay; thin filament calcium reporter; RNA sequencing; NPPB transcriptional reporter Circulation High 33025817
2021 The HCM-associated TNNT2 variant I79N significantly increases myofilament Ca2+ sensitivity and decreases the Ca2+ off-rate constant (koff) in reconstituted human cardiac thin filaments; in heterozygous I79N+/- hiPSC-CMs, enhanced cytosolic Ca2+ buffering reduced Ca2+ transients, causing beat-to-beat instability, action potential triangulation, and voltage/Ca2+ alternans at higher stimulation frequencies, mechanistically linking the variant to arrhythmogenesis. Reconstituted human cardiac thin filaments with steady-state and stopped-flow fluorescence; CRISPR/Cas9-generated I79N+/- hiPSC-CMs; voltage and Ca2+ transient measurement; NanoString transcriptomics Frontiers in cell and developmental biology High 34977031
2022 The TNNT2 Δ160E mutation causes sarcomeric calcium retention, prolonged calcium decay, relaxation impairment, and cardiomyocyte hypertrophy in isogenic hiPSC-CMs in a dose-dependent manner; the mutation promotes hypertrophic signaling via NFATc1 nuclear translocation and increased CaMKIIδ and phospholamban phosphorylation; calcium desensitization with epigallocatechin-3-gallate rescues the prolonged calcium decay phenotype. CRISPR/Cas9 isogenic iPSC-CMs (hetero- and homozygous); calcium transient measurement; high-content imaging of NFATc1 nuclear translocation; western blotting for CaMKIIδ and phospholamban phosphorylation; R-GECO-fused mutant troponin T overexpression Circulation. Genomic and precision medicine High 35861968
2022 The TNNT2 K280N mutation increases myofilament Ca2+ sensitivity independently of phosphorylation status (not corrected by alkaline phosphatase or PKA treatment); as little as 14% mutant cTnT-K280N in troponin exchange experiments is sufficient to elevate Ca2+ sensitivity; homozygous K280N hiPSC-CMs show elevated diastolic Ca2+, enhanced contractility, and impaired relaxation. Force measurements in isolated cardiomyocytes from homozygous K280N patient; troponin exchange experiments; alkaline phosphatase and PKA treatment; CRISPR/Cas9 isogenic hiPSC-CMs; Ca2+ transient and cell shortening assays Journal of molecular and cellular cardiology plus High 37159677
2022 DYRK1A overexpression in iPSC-derived cardiomyocytes increases the abundance of TNNT2 fetal splice variants by ~58% and decreases the adult cTnT3 variant by ~27%, with increased SRSF6 phosphorylation (~25-65%), establishing that DYRK1A regulates TNNT2 alternative splicing through phosphorylation of the splicing factor SRSF6. iPSC-derived cardiomyocytes with DYRK1A overexpression; RT-PCR for TNNT2 splice variants; phospho-SRSF6 western blotting Cardiovascular toxicology Medium 35596909
2019 In zebrafish, tnnt2a is expressed not only in myocardial cells but also in a novel group of myl7-negative smooth muscle cells on the outflow tract (OFT); restoration of tnnt2a expression in myocardial tissue alone (via myl7 promoter) was insufficient to recover normal heart function and circulation, whereas combinatorial rescue in both myocardial and OFT cells fully restored cardiac function, demonstrating that TNNT2 expression in OFT smooth muscle cells is indispensable for normal cardiac mechanical dynamics. CRISPR/Cas9 tnnt2a zebrafish mutants; conditional/inducible promoter-driven rescue; RNA-seq; immunofluorescence; cardiac function imaging Biology open Medium 31796423
2021 XIN protein expression is reduced in TNNT2-ΔK210 hESC-derived cardiomyocytes and mouse heart tissues; overexpression of XINB decreases myofilament disorganization and increases cell contractility in TNNT2-ΔK210 cardiomyocytes; AAV9-mediated cardiac XINB overexpression in TNNT2-ΔK210 mice partially reversed cardiac dilation, systolic dysfunction, and fibrosis. hESC-derived cardiomyocytes; TNNT2-ΔK210 mouse model; AAV9 cardiac overexpression; echocardiography; histology Frontiers in cell and developmental biology Medium 34222259
2019 In Down syndrome myocardium, the DYRK1A-SRSF6-TNNT2 pathway is dysregulated: phosphorylated SRSF6 levels are 2.6-fold higher in trisomic myocardium, and fetal TNNT2 splice variants are more highly expressed, consistent with trisomy 21 gene dosage effects driving aberrant TNNT2 splicing via SRSF6 hyperphosphorylation. Western blotting for phospho-DYRK1A, phospho-SRSF6; RT-PCR/analysis of TNNT2 fetal isoforms in human myocardial tissue samples Experimental and molecular pathology Medium 31201803
2022 The HCM-linked TNNT2 mutation R92Q causes increased myofilament calcium sensitivity in atrial muscle, leading to reduced inotropic reserve, slower twitch kinetics, and increased spontaneous beats and triggered contractions representing an intrinsic atrial arrhythmogenic mechanism; by contrast, the E163R mutation increases energy cost of tension generation in atrial muscle without causing atrial arrhythmic propensity, establishing genotype-specific atrial pathomechanisms. HCM mouse models (R92Q and E163R); atrial trabecula functional assays (twitch amplitude, kinetics, ATP consumption, myofilament calcium sensitivity); echocardiography Frontiers in physiology Medium 35514357
2023 The HCM-linked TNNT2 mutation R92L allosterically repositions the N-terminus of cTnI closer to cTnC (measured by TR-FRET), creates additional electrostatic interactions at the PKA consensus sequence, and reduces cTnI phosphorylation at that site, thereby impairing PKA-mediated regulation of myofilament relaxation and causing early-onset diastolic dysfunction; constitutive phosphomimetic cTnI (D23D24) rescued diastolic function only for R92L but not Δ160E. In vivo mouse models; ex vivo hemodynamics; stopped-flow kinetics; time-resolved FRET (TR-FRET); molecular dynamics simulations; western blotting; 2D echocardiography bioRxivpreprint Medium 37503299
2026 The TNNT2-R151W mutation causes sarcomere disarray, attenuated Ca2+ transient amplitude, prolonged time to peak, and delayed decay tau in patient-derived iPSC-CMs, with substantially decreased contractile force in pillar-based engineered heart tissue; overexpression of wild-type TNNT2 rescued all these phenotypes, providing functional evidence that the mutation causes pediatric DCM through sarcomere insufficiency and Ca2+ handling disturbances. Patient-derived iPSC-CMs; pillar-based engineered heart tissue (EHT) contractile force assay; Ca2+ transient imaging; wild-type TNNT2 overexpression rescue Bioengineering & translational medicine Medium 42016857
2024 The TNNT2 R141W mutation (modeled as Tnnt2 R154W in mice) causes LVNC through loss of a salt bridge between TNNT2(R141W) and E-257 in tropomyosin (identified by 3D protein structural modeling), decreasing cardiac contraction; furthermore, nuclear TNNT2 functions as an HDAC1 sponge in cardiomyocyte nuclei, and the R141W mutation compromises this nuclear TNNT2-HDAC1 association, causing epigenetic perturbation and transcriptional dysregulation; simvastatin restores the nuclear TNNT2(R141W)-HDAC1 association and recovers cardiac function. Knock-in mice (Tnnt2 R154W); iPSC-derived cardiomyocytes from LVNC patients; 3D protein structure modeling; co-immunoprecipitation (nuclear TNNT2-HDAC1); omics analysis; pharmacological rescue with simvastatin, pan-HDAC inhibitor, TGFβR1 inhibitor, EZH2 inhibitor bioRxivpreprint Medium
2023 TNNT2 protein physically interacts with EGFR in colorectal cancer cells (demonstrated by co-immunoprecipitation); TNNT2 overexpression upregulates EGFR and HER2 expression, decreases E-cadherin, and increases Vimentin and N-cadherin, promoting EMT; knockdown reverses these effects, suggesting TNNT2 promotes CRC invasion through an EGFR/HER2/EMT signaling axis. Co-immunoprecipitation; western blotting; CCK-8; colony formation; Transwell assay; qPCR Cancer cell international Low 37481519
2025 In hiPSC-CMs bearing HCM (hypercontractile) or DCM (hypocontractile) TNNT2 pathogenic variants, impaired contractile transients alter lamin A/C expression and nuclear stiffness (nuclear lamina remodeling); treatment with myosin modulators Mavacamten (for HCM) or Omecamtiv Mecarbil (for DCM) rescued these changes in nuclear stiffness, establishing a causal link between sarcomere contractility and nuclear mechanics. hiPSC-CMs with TNNT2 pathogenic variants; transcriptomics; nuclear stiffness measurements; pharmacological rescue with Mavacamten and Omecamtiv Mecarbil iScience Medium 41321620

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clinical and translational science 159 19412328
2009 Clinical and functional characterization of TNNT2 mutations identified in patients with dilated cardiomyopathy. Circulation. Cardiovascular genetics 94 20031601
1994 Human cardiac troponin T: identification of fetal isoforms and assignment of the TNNT2 locus to chromosome 1q. Genomics 67 8088824
2009 [Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy]. Revista espanola de cardiologia 59 19150014
2010 Severe familial left ventricular non-compaction cardiomyopathy due to a novel troponin T (TNNT2) mutation. Cardiovascular research 58 20083571
2003 Hypertrophic cardiomyopathy: low frequency of mutations in the beta-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes among Spanish patients. Clinical chemistry 57 12881443
2020 Development of a Cardiac Sarcomere Functional Genomics Platform to Enable Scalable Interrogation of Human TNNT2 Variants. Circulation 52 33025817
2013 Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy. American heart journal 48 24093860
2018 Intercalated cushion cells within the cardiac outflow tract are derived from the myocardial troponin T type 2 (Tnnt2) Cre lineage. Developmental dynamics : an official publication of the American Association of Anatomists 34 29920846
2010 Inducible cardiomyocyte-specific gene disruption directed by the rat Tnnt2 promoter in the mouse. Genesis (New York, N.Y. : 2000) 29 20014345
2017 Digenic inheritance of mutations in the cardiac troponin (TNNT2) and cardiac beta myosin heavy chain (MYH7) as the cause of severe dilated cardiomyopathy. European journal of medical genetics 27 28642161
2004 The role of a common TNNT2 polymorphism in cardiac hypertrophy. Journal of human genetics 27 14986170
2020 Increased Myocardial Oxygen Consumption Precedes Contractile Dysfunction in Hypertrophic Cardiomyopathy Caused by Pathogenic TNNT2 Gene Variants. Journal of the American Heart Association 24 32290750
2021 Mechanisms of Arrhythmogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (TNNT2) Variant I79N. Frontiers in cell and developmental biology 22 34977031
2013 The genetics of dilated cardiomyopathy: a prioritized candidate gene study of LMNA, TNNT2, TCAP, and PLN. Clinical cardiology 22 24037902
2013 Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy. Circulation journal : official journal of the Japanese Circulation Society 20 23782526
2022 Genotype-Driven Pathogenesis of Atrial Fibrillation in Hypertrophic Cardiomyopathy: The Case of Different TNNT2 Mutations. Frontiers in physiology 17 35514357
2009 The role of large gene deletions and duplications in MYBPC3 and TNNT2 in patients with hypertrophic cardiomyopathy. International journal of cardiology 15 19666196
2011 Cardiac Troponin T (TNNT2) mutations are less prevalent in Indian hypertrophic cardiomyopathy patients. DNA and cell biology 14 22017532
2021 Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy. Forensic science international. Genetics 13 33588347
2020 A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy. Frontiers in physiology 13 33304277
2019 Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish. Biology open 12 31796423
2019 TNNT2 Missplicing in Skeletal Muscle as a Cardiac Biomarker in Myotonic Dystrophy Type 1 but Not in Myotonic Dystrophy Type 2. Frontiers in neurology 11 31611837
2016 Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study. Arquivos brasileiros de cardiologia 11 27737317
2009 Dilated cardiomyopathy caused by a novel TNNT2 mutation-added value of genetic testing in the correct identification of affected subjects. International journal of cardiology 11 19324435
2022 Human-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for TNNT2 Δ160E-Induced Cardiomyopathy. Circulation. Genomic and precision medicine 10 35861968
2021 Cardiac Overexpression of XIN Prevents Dilated Cardiomyopathy Caused by TNNT2 ΔK210 Mutation. Frontiers in cell and developmental biology 9 34222259
2012 Genetic variation screening of TNNT2 gene in a cohort of patients with hypertrophic and dilated cardiomyopathy. Physiological research 9 22292720
2016 Molecular and in silico analysis of a new plasmid-mediated AmpC β-lactamase (CMH-2) in clinical isolates of Klebsiella pneumoniae. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 8 27964935
2015 TNNT2 Gene Polymorphisms are Associated with Susceptibility to Idiopathic Dilated Cardiomyopathy in Kazak and Han Chinese. Medical science monitor : international medical journal of experimental and clinical research 8 26525169
2019 Comparative analysis of the DYRK1A-SRSF6-TNNT2 pathway in myocardial tissue from individuals with and without Down syndrome. Experimental and molecular pathology 7 31201803
2023 Cardiac tropoini T (TNNT2) plays a potential oncogenic role in colorectal carcinogenesis. Cancer cell international 6 37481519
2022 Low expression of the K280N TNNT2 mutation is sufficient to increase basal myofilament activation in human hypertrophy cardiomyopathy. Journal of molecular and cellular cardiology plus 6 37159677
2014 Cardiac troponin T (TNNT2) mutations in chinese dilated cardiomyopathy patients. BioMed research international 6 25110706
2006 Hypertrophic cardiomyopathy--molecular genetic analysis of exons 9 and 11 of the TNNT2 gene in Czech patients. Methods of information in medicine 6 16538283
2025 The p.Asn271Ile Variant in the TNNT2 Gene Is Associated With Low-Risk Late-Onset Hypertrophic Cardiomyopathy. JACC. Heart failure 5 40310325
2023 Tale of two hearts: a TNNT2 hypertrophic cardiomyopathy case report. Frontiers in cardiovascular medicine 5 37180798
2013 TNNT2 gene polymorphisms are associated with susceptibility to idiopathic dilated cardiomyopathy in the Han Chinese population. BioMed research international 5 23586019
2017 Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death. Pediatric cardiology 4 28669108
2020 A novel nonsense mutation in TNNT2 in a Chinese pedigree with hypertrophic cardiomyopathy: A case report. Medicine 3 32846832
2025 Phenotype specific nuclear lamina remodeling in hiPSC derived cardiomyocytes bearing TNNT2 sarcomeric variants. iScience 2 41321620
2023 Human induced pluripotent stem cell line YCMi007-A generated from a dilated cardiomyopathy patient with a heterozygous dominant c.613C > T (p. Arg205Trp) variant of the TNNT2 gene. Stem cell research 2 36801602
2022 Impact of DYRK1A Expression on TNNT2 Splicing and Daunorubicin Toxicity in Human iPSC-Derived Cardiomyocytes. Cardiovascular toxicology 2 35596909
2012 [Expression of ACTN2, alpha-actin and TNNT2 in rat bone marrow-derived mesenchymal stem cells induced by low frequency pulsed electromagnetic fields]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 2 23230735
2025 Cardiac-Specific Gene Editing via an AAV9-Tnnt2-SaCas9-miR122TS Vector. Bio-protocol 1 40084085
2025 Generation of a human embryonic stem cell line (WAe009-A-3B) carrying homozygous TNNT2 gene knockout by CRISPR/Cas9 editing. Stem cell research 1 40344932
2024 Carrying both the heterozygous Myh6-R453C and Tnnt2-R92W mutations aggravate the hypertrophic cardiomyopathy phenotype in mice. Biochemical and biophysical research communications 1 39191188
2021 Generation of an iPSC line (ZZUNEUi021-A) from a hypertrophic cardiomyopathy patient with TNNT2 mutation. Stem cell research 1 34929444
2020 Chondroid and Osseous Metaplasia of the Central Fibrous Body in Adolescent Hearts with Mutations in TNNI3 and TNNT2 genes. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 1 32758068
2026 A TNNT2 variant in a sporadic case of dilated cardiomyopathy: a case report and review. Frontiers in cardiovascular medicine 0 41969674
2026 Pediatric dilated cardiomyopathy caused by TNNT2-R151W mutation: Modeling and rescue in patient-derived induced pluripotent stem cells and engineered heart tissue. Bioengineering & translational medicine 0 42016857
2025 Generation of an induced pluripotent stem cell line (HPCHi002-A) derived from a dilated cardiomyopathy patient harboring heterozygous mutations c.644G > T (p.Arg215Leu) in the TNNT2 gene. Stem cell research 0 41429711
2023 The HCM - Linked Mutation Arg92Leu in TNNT2 Allosterically Alters the cTnC - cTnI Interface and Disrupts the PKA-mediated Regulation of Myofilament Relaxation. bioRxiv : the preprint server for biology 0 37503299
2022 A case of fetal isolated ventricular noncompaction with TNNT2 gene mutation and literature review. Echocardiography (Mount Kisco, N.Y.) 0 36229763
2008 [Association of TNNT2 gene mutations with idiopathic dilated cardiomyopathy in a Chengdu population]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 19253838
2006 [Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype]. Zhonghua xin xue guan bing za zhi 0 16630449

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