TTN
Chr 2ADARtitin
Also known as: CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC, HMERF, LGMD2J
The protein encoded by this gene is titin, a giant structural protein that spans half the length of a sarcomere and provides elasticity to striated muscle while serving as a template for assembly of contractile machinery. Mutations cause a spectrum of muscle diseases including hypertrophic and dilated cardiomyopathies, congenital myopathy with cardiomyopathy, limb-girdle muscular dystrophy, myofibrillar myopathy with early respiratory failure, and tibial muscular dystrophy. The disorders follow both autosomal dominant and autosomal recessive inheritance patterns, with pathogenicity resulting from disruption of sarcomere structure and muscle elasticity.
Definitive — sufficient evidence for diagnostic panels
6 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TTN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Urinary Titin Biomarker in DMD
RECRUITINGSpastic Myopathy in Adults With Cerebral Palsy
RECRUITINGBiomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)
RECRUITINGClinical and Functional Assessment of Patients With Inherited Non-Duchenne Myopathies in Sohag University Hospital
RECRUITINGAnticoagulation in ICH Survivors for Stroke Prevention and Recovery
RECRUITINGImproving Vaccine Protection for Older Adults
RECRUITINGDefining the Risk of Ventricular Tachycardia in Genetic Cardiomyopathies
RECRUITINGOxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools