Gene: TTN
Alternate names for this Gene: CMD1G|CMH9|CMPD4|EOMFC|HMERF|LGMD2J|LGMDR10|MYLK5|SALMY|TMD
Gene Summary: This gene encodes a large abundant protein of striated muscle. The product of this gene is divided into two regions, a N-terminal I-band and a C-terminal A-band. The I-band, which is the elastic part of the molecule, contains two regions of tandem immunoglobulin domains on either side of a PEVK region that is rich in proline, glutamate, valine and lysine. The A-band, which is thought to act as a protein-ruler, contains a mixture of immunoglobulin and fibronectin repeats, and possesses kinase activity. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Alternative splicing of this gene results in multiple transcript variants. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Mutations in this gene are associated with familial hypertrophic cardiomyopathy 9, and autoantibodies to titin are produced in patients with the autoimmune disease scleroderma.
Gene is located in Chromosome: 2
Location in Chromosome : 2q31.2
Description of this Gene: titin
Type of Gene: protein-coding
rs28933405 in
TTN gene and
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 9
PMID 21267010 2011 Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14).
PMID 10462489 1999 Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene.
rs267607155 in
TTN gene and
Cardiomyopathy, Dilated
PMID 11788824 2002 Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy.
PMID 28941705 2017 Severe DCM phenotype of patient harboring RBM20 mutation S635A can be modeled by patient-specific induced pluripotent stem cell-derived cardiomyocytes.
PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.
PMID 10051295 1999 Familial dilated cardiomyopathy locus maps to chromosome 2q31.
PMID 26315439 2015 HEART DISEASE. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.
rs139517732 in
TTN gene and
Cardiomyopathy, Dilated, 1g
PMID 11788824 2002 Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy.
PMID 11846417 2002 Titin mutations as the molecular basis for dilated cardiomyopathy.
PMID 16465475 2005 Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy.
rs10497522 in
TTN gene and
Leukemia, Myelocytic, Acute
PMID 27903959 2017 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.
rs55863869 in
TTN gene and
QT interval feature (observable entity)
PMID 29213071 2017 GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.
rs1489486 in
TTN gene and
Systolic Pressure
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.