TNNT1

Chr 19ARAD

troponin T1, slow skeletal type

Also known as: ANM, NEM5, STNT, TNT, TNTS

Encodes slow skeletal troponin T, which binds tropomyosin and regulates striated muscle contraction in response to intracellular calcium fluctuations as part of the troponin complex. Mutations cause nemaline myopathy type 5, presenting as severe infantile disease with respiratory insufficiency and death by age 2 years (autosomal recessive) or milder childhood-onset forms (autosomal recessive or dominant inheritance). The pathogenic mechanism involves rod-shaped nemaline inclusions in skeletal muscle fibers leading to progressive muscle weakness.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
DNmechanismAR/ADLOEUF 1.483 OMIM phenotypes
Clinical SummaryTNNT1
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Gene-Disease Validity (ClinGen)
nemaline myopathy 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.48LOEUF
pLI 0.000
Z-score -0.08
OE 1.02 (0.721.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.99Z-score
OE missense 0.79 (0.690.91)
139 obs / 176.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.02 (0.721.48)
00.351.4
Missense OE0.79 (0.690.91)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 20 / 19.6Missense obs/exp: 139 / 176.0Syn Z: -0.32
DN
0.79top 25%
GOF
0.5367th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TNNT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ResilienceCognitive Function and Well-BeingMuscle Function, Handgrip Strength Test

Aging Resilience Through Microbiota Optimization and Regulation

ACTIVE NOT RECRUITING
NCT06649981Phase PHASE1Gonzalo Jorquera, PhDStarted 2025-01-10
FMT capsulePlacebo Capsule(s)
ICI-myocarditis

Genetic Determinants of Myocarditis Induced by Immune-checkpoint Inhibitors

RECRUITING
NCT06734689Assistance Publique - Hôpitaux de ParisStarted 2025-09-23
IUGRFetal Growth RetardationIntrauterine Growth Restriction

Cardiac Displacement From Third Trimester to Early Childhood

ACTIVE NOT RECRUITING
NCT02583763University Hospital, LinkoepingStarted 2013-01
EchocardiographyBlood sample
Malignant NeoplasmOrgan Damage

Construction and Evaluation of Tumor Immunotherapy and Organ Damage Early Warning System Based on Multi-omics

RECRUITING
NCT07131007Hebei Medical University Fourth HospitalStarted 2025-09-15
Immunotherapy Monitoring and Sample Collection
Hereditary Amyloidosis, Transthyretin-Related

Phenotypic Manifestations of Hereditary ATTR Amyloidosis

RECRUITING
NCT07124377Hospital 9 de Julio de Las BreñasStarted 2024-09-01
A complete physical examination of all body systems, including height and body weightNeurological examination includes motor strength testing; sensory testing with pinprick, light touch, temperature, and proprioception; deep tendon reflexes; and gait assessment.Electrocardiogram (12-lead ECG)
Postoperative ComplicationsMultiple Organ FailureAbdominal Surgery

Dalargin for Prevention of Organ Disfunction in High-Risk Abdominal Surgery

ACTIVE NOT RECRUITING
NCT07404358Phase PHASE3Botkin HospitalStarted 2025-05-13
Dalargin0.9 % NaCl
Heart FailureAmyloid CardiomyopathyATTR Amyloidosis Wild Type

EOSS-ATTR Study (eHealth Based Operative Support System in ATTR-CM)

NOT YET RECRUITING
NCT06499064Phase NAHospital Universitari de BellvitgeStarted 2024-12-01
mHealth
Amyloidosis in Transthyretin (TTR)Amyloidosis, Familial

Comprehensive Program for Hereditary Transthyretin Amyloidosis

RECRUITING
NCT07213297Hospital de Alta Complejidad en RedStarted 2025-11-01
clinical assessments and complementary examinations
TNNT1-associated MyopathyInfantile-onset Nemaline Rod MyopathyMyopathies, Nemaline

WiTNNess - TNNT1 Myopathy Natural History Study

RECRUITING
NCT06374719Clinic for Special ChildrenStarted 2018-09-23
Silent Myocardial IschemiaAcute Myocardial Infarction

Silent Myocardial Ischemia in Patients Undergoing Non-oncological Abdominal Surgeries

RECRUITING
NCT06536686University Medical Centre LjubljanaStarted 2024-07-01
Silent myocardial ischemia, STEMI
Heart FailureDilated Cardiomyopathy

Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

ACTIVE NOT RECRUITING
NCT05837143Phase EARLY_PHASE1Shanghai East HospitalStarted 2023-03-30
JV001
Chronic Heart FailureAging

Comparing the Effects of Combining Cognitive and Physical Exercise Training on Cognition, and Cerebral Blood Flow Regulation in Men and Women With Chronic Heart Failure

RECRUITING
NCT04970888Phase NAMontreal Heart InstituteStarted 2021-09-01
Cognitive trainingExercise trainingUsual care
Clinical Literature
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Full-Text Mentions
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