TTN Chromosome 2
Titin
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What This Gene Does
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. [provided by RefSeq, Feb 2012]
Gene Info
Gene Group
"Fibronectin type III domain containing|I-set domain containing|Myosin light chain kinase family"
Locus Type
gene with protein product
Location
2q31.2
Ensembl
ENSG00000155657
Associated Conditions (130)
Dilated cardiomyopathy 1G
Autosomal recessive limb-girdle muscular dystrophy type 2J
Cardiovascular phenotype
Hypertrophic cardiomyopathy 9
Myopathy
myofibrillar
9
with early respiratory failure
Tibial muscular dystrophy
Early-onset myopathy with fatal cardiomyopathy
Cardiomyopathy
TTN-related disorder
6 conditions
Primary dilated cardiomyopathy
Hypertrophic cardiomyopathy
Long QT syndrome
Areflexia of lower limbs
Spinal rigidity
Thoracic kyphoscoliosis
Bilateral talipes equinovarus
+110 more conditions
Key Variants
RS1004455055
Conflicting classifications of pathogenicity
Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype
Health Risk
RS1005082526
Conflicting classifications of pathogenicity
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J
Health Risk
RS1006806821
Conflicting classifications of pathogenicity
Hypertrophic cardiomyopathy 9, Autosomal recessive limb-girdle muscular dystrophy type 2J, Myopathy
Health Risk
RS1007434751
Conflicting classifications of pathogenicity
Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G
Health Risk
RS1010541689
Conflicting classifications of pathogenicity
Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G
Health Risk
RS1012929202
Conflicting classifications of pathogenicity
Cardiovascular phenotype, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G
Health Risk
RS1015506783
Conflicting classifications of pathogenicity
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Cardiovascular phenotype
Health Risk
RS1016165797
Conflicting classifications of pathogenicity
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Cardiomyopathy
Health Risk
RS10200398
Conflicting classifications of pathogenicity
Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Early-onset myopathy with fatal cardiomyopathy
Health Risk
RS1020838415
Conflicting classifications of pathogenicity
Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G
Health Risk
RS1021499065
Conflicting classifications of pathogenicity
Cardiovascular phenotype, Cardiovascular phenotype
Health Risk
RS1023726354
Conflicting classifications of pathogenicity
Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J
Health Risk
All Variants (7833)
| RSID | Category | Clinical Significance | Conditions |
|---|---|---|---|
| RS2154138232 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154139241 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154139263 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154139293 | Health Risk | Likely pathogenic | Neurodevelopmental delay, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154139316 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154139357 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154139399 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154139656 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154139897 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154140017 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154140040 | Health Risk | Likely pathogenic | Primary familial dilated cardiomyopathy, Primary familial dilated cardiomyopathy |
| RS2154140054 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154140080 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154140145 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154140269 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154140292 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154140546 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154141555 | Health Risk | Likely pathogenic | — |
| RS2154141588 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154141656 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154142418 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154142450 | Health Risk | Likely pathogenic | — |
| RS2154142487 | Health Risk | Likely pathogenic | Tip-toe gait, Tip-toe gait |
| RS2154142563 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154142586 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154142938 | Health Risk | Likely pathogenic | Cardiovascular phenotype, Cardiovascular phenotype |
| RS2154142958 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154143307 | Health Risk | Likely pathogenic | Cardiovascular phenotype, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154143363 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154143380 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154143418 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154143419 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154143564 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Dilated cardiomyopathy 1G |
| RS2154143867 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154144138 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154144335 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154145062 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154145209 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154145442 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154145523 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154145603 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Primary dilated cardiomyopathy |
| RS2154145628 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154145769 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154145784 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154145831 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Cardiovascular phenotype |
| RS2154146389 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154146720 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |
| RS2154146843 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154146971 | Health Risk | Likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J |
| RS2154147379 | Health Risk | Likely pathogenic | Dilated cardiomyopathy 1G, Autosomal recessive limb-girdle muscular dystrophy type 2J, Dilated cardiomyopathy 1G |