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

Gene: TTN-AS1

Alternate names for this Gene: -

Gene Summary: This gene encodes a non-coding RNA transcribed from the opposite strand to the titin gene.

Gene is located in Chromosome: 2

Location in Chromosome : 2q31.2

Description of this Gene: TTN antisense RNA 1

Type of Gene: ncRNA

rs12614435 in TTN;TTN-AS1 gene and Atrial Fibrillation PMID 29290336 2018 Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development.

PMID 30061737 2018 Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.

PMID 29892015 2018 Multi-ethnic genome-wide association study for atrial fibrillation.

rs574660186 in TTN;TTN-AS1 gene and CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 9 PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

rs140743001 in TTN;TTN-AS1 gene and Cardiomyopathy, Dilated PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

PMID 24503780 2014 The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

PMID 25589632 2015 Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

PMID 23418287 2013 Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

PMID 16733766 2006 Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy.

PMID 30536954 2019 Neuromuscular transmission defects in myopathies: Rare but worth searching for.

PMID 24119082 2013 Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy.

PMID 15802564 2005 The kinase domain of titin controls muscle gene expression and protein turnover.

PMID 12145747 2002 Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.

PMID 18948003 2008 Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

PMID 17444505 2007 C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy.

PMID 25163546 2015 Atlas of the clinical genetics of human dilated cardiomyopathy.

PMID 26899768 2016 Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation.

rs1057518195 in TTN;TTN-AS1 gene and Cardiomyopathy, Dilated, 1g PMID 24395473 2014 Atypical phenotypes in titinopathies explained by second titin mutations.

PMID 23975875 2013 Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.

PMID 25589632 2015 Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

PMID 18948003 2008 Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

PMID 27813223 2017 Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy.

PMID 26084686 2015 Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy.

PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

PMID 26701604 2015 Prevalence of Titin Truncating Variants in General Population.

PMID 21520333 2011 LOVD v.2.0: the next generation in gene variant databases.

PMID 23418287 2013 Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

PMID 17444505 2007 C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy.

PMID 29057560 2018 The first titin (c.59926 + 1G > A) founder mutation associated with dilated cardiomyopathy.

PMID 24119082 2013 Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy.

PMID 26899768 2016 Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation.

PMID 25163546 2015 Atlas of the clinical genetics of human dilated cardiomyopathy.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 27353043 2016 Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

rs1553742630 in TTN;TTN-AS1 gene and Centronuclear myopathy PMID 25589632 2015 Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

rs574660186 in TTN;TTN-AS1 gene and Hereditary Myopathy with Early Respiratory Failure PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

rs10171049 in TTN;TTN-AS1 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.

rs1057518195 in TTN;TTN-AS1 gene and MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2J PMID 18948003 2008 Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

PMID 23975875 2013 Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.

PMID 24395473 2014 Atypical phenotypes in titinopathies explained by second titin mutations.

PMID 25589632 2015 Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

PMID 27813223 2017 Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy.

PMID 26084686 2015 Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy.

PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

PMID 26701604 2015 Prevalence of Titin Truncating Variants in General Population.

PMID 26777568 2016 Relevance of truncating titin mutations in dilated cardiomyopathy.

PMID 21520333 2011 LOVD v.2.0: the next generation in gene variant databases.

PMID 23418287 2013 Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

PMID 17444505 2007 C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy.

PMID 29057560 2018 The first titin (c.59926 + 1G > A) founder mutation associated with dilated cardiomyopathy.

PMID 24119082 2013 Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy.

PMID 25163546 2015 Atlas of the clinical genetics of human dilated cardiomyopathy.

PMID 26899768 2016 Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 27353043 2016 Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders.

rs1553650442 in TTN;TTN-AS1 gene and Multiple congenital anomalies PMID 10462489 1999 Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene.

PMID 21810661 2011 Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes.

PMID 23418287 2013 Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

PMID 11717165 2001 The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.

PMID 21617319 2011 Contribution of genetic factors to the pathogenesis of dilated cardiomyopathy: the cause of dilated cardiomyopathy: genetic or acquired? (genetic-side).

PMID 24105469 2014 Recessive TTN truncating mutations define novel forms of core myopathy with heart disease.

PMID 18948003 2008 Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

PMID 12669942 2003 Left ventricular systolic dysfunction and ischemic cardiomyopathy.

PMID 24395473 2014 Atypical phenotypes in titinopathies explained by second titin mutations.

PMID 23518707 2013 Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2.

PMID 1745277 1991 Muscular dystrophy with separate clinical phenotypes in a large family.

PMID 12145747 2002 Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.

PMID 17444505 2007 C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy.

rs878854324 in TTN;TTN-AS1 gene and Muscle hypotonia PMID 21810661 2011 Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes.

PMID 21617319 2011 Contribution of genetic factors to the pathogenesis of dilated cardiomyopathy: the cause of dilated cardiomyopathy: genetic or acquired? (genetic-side).

PMID 17444505 2007 C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy.

PMID 12669942 2003 Left ventricular systolic dysfunction and ischemic cardiomyopathy.

PMID 18948003 2008 Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).

PMID 1745277 1991 Muscular dystrophy with separate clinical phenotypes in a large family.

PMID 11717165 2001 The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.

PMID 12145747 2002 Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.

PMID 10462489 1999 Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification of a novel disease gene.

PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

PMID 23418287 2013 Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

PMID 24105469 2014 Recessive TTN truncating mutations define novel forms of core myopathy with heart disease.

PMID 24395473 2014 Atypical phenotypes in titinopathies explained by second titin mutations.

PMID 23518707 2013 Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2.

rs574660186 in TTN;TTN-AS1 gene and Myopathy, Early-Onset, with Fatal Cardiomyopathy PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.

rs397517481 in TTN;TTN-AS1 gene and Neuromuscular Diseases PMID 23975875 2013 Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.

rs281864928 in TTN;TTN-AS1 gene and TIBIAL MUSCULAR DYSTROPHY, TARDIVE PMID 12891679 2003 Tibial muscular dystrophy in a Belgian family.

PMID 12145747 2002 Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.

PMID 22335739 2012 Truncations of titin causing dilated cardiomyopathy.