Home > Gene Browser > TTN

TTN

Synonyms
CMD1G, CMH9, CMPD4, EOMFC, HMERF, LGMD2J, LGMDR10, MYLK5, SALMY, TMD
External resources
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.

Variant counts

The variants found in rare patients tested by 3billion are classified and counted according to ACMG guidelines. The variants with over 5% variant frequency in population genome databases ( gnomAD, dbSNP, etc) are excluded.

Pathogenic
443
Likely pathogenic
11
VUS
127,684
Likely benign
117,553
Benign
8,765

Patient phenotypes

Proportions of phenotypes among 369 patients carrying pathogenic or likely pathogenic variants on TTN gene are displayed below.

Phenotype class
Patients in 3billion (%)
Abnormality of the nervous system
38.2%
Abnormality of the musculoskeletal system
28.5%
Abnormality of head or neck
19.8%
Abnormality of the cardiovascular system
19.2%
Abnormality of the eye
18.7%
Abnormality of the ear
14.1%
Abnormality of limbs
13.8%
Growth abnormality
13.8%
Abnormality of the genitourinary system
9.8%
Abnormality of the integument
8.9%
Abnormality of the digestive system
7%
Abnormality of the immune system
5.4%
Abnormality of the endocrine system
3.5%
Abnormality of blood and blood-forming tissues
3.3%
Abnormality of the respiratory system
3.3%
Abnormality of prenatal development or birth
3%
Neoplasm
1.9%
Abnormal cellular phenotype
0.8%
Abnormality of the breast
0.8%
Constitutional symptom
0.8%
Abnormality of the voice
0.5%
Abnormality of metabolism homeostasis
0%
Abnormality of the thoracic cavity
0%

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