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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TTN Gene

protein-coding GIFtS: 66
GCID: GC02M179355

titin

(Previous names: cardiomyopathy, dilated 1G (autosomal dominant) )
(Previous symbol: CMD1G)

Explore 49 diseases affiliated with
TTN via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Titin¹		EOMFC² ⁵
CMD1G¹ ² ⁵		HMERF² ⁵
LGMD2J¹ ² ⁵		FLJ32040¹
TMD¹ ² ⁵		Cardiomyopathy, Dilated 1G (Autosomal Dominant)¹
CMH9¹ ²		Connectin³
CMPD4¹ ²		Connectin³
MYLK5¹ ²		EC 2.7.11.1³
Rhabdomyosarcoma Antigen MU-RMS-40.14² ³		MPRM⁵

External Ids:	HGNC: 12403¹	Entrez Gene: 7273²	Ensembl: ENSG00000155657⁷	OMIM: 188840⁵	UniProtKB: Q8WZ42³

Export aliases for TTN gene to outside databases

Previous GC identifers: GC02M177454 GC02M178061 GC02M179593 GC02M179216 GC02M179098 GC02M171261

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TTN:

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)

UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42

Function: Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the

level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the

sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility

properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation

during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase

Gene Wiki entry for TTN (Titin)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_005403.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TTN gene promoter:
STAT1 HNF-1 STAT1beta IRF-1 STAT1alpha HNF-1A
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TTN promoter sequence

Search SABiosciences Chromatin IP Primers for TTN

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TTN

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q31 Ensembl cytogenetic band: 2q31.2 HGNC cytogenetic band: 2q31

TTN Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TTN gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M179355: view genomic region (about GC identifiers)

Start:	179,390,716 bp from pter	End:	179,695,529 bp from pter
Size:	304,814 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42 (See protein sequence)

Recommended Name: Titin

Size: 34350 amino acids; 3816030 Da

Cofactor: Magnesium

Subunit: Interacts with MYOM1, MYOM2, tropomyosin and myosin. Interacts with actin, primarily via the PEVK domains and

with MYPN (By similarity). Interacts with FHL2, NEB, CRYAB, LMNA/lamin-A and LMNB/lamin-B. Interacts with

TCAP/telethonin and/or ANK1 isoform Mu17/ank1.5, via the first two N-terminal immunoglobulin domains. Interacts with

TRIM63 and TRIM55, through several domains including immunoglobulin domains 141 and 142. Interacts with ANKRD1, ANKRD2

and ANKRD23, via the region between immunoglobulin domains 77 and 78 and interacts with CAPN3, via immunoglobulin

domain 79. Interacts with NBR1 through the protein kinase domain. Interacts with CALM/calmodulin. Isoform 6 interacts

with OBSCN isoform 3. Interacts with CMYA5

Subcellular location: Cytoplasm (Probable). Nucleus

Miscellaneous: In some isoforms, after the PEVK repeat region there is a long PEVK duplicated region. On account of

this region, it has been very difficult to sequence the whole protein. The length of this region (ranging from 183 to

2174 residues), may be a key elastic element of titin

Sequence caution: Sequence=AAH58824.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A

sequence starting in position 553; Sequence=AAH70170.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.

Potential poly-A sequence starting in position 627; Sequence=CAA62188.1; Type=Frameshift; Positions=17036, 17043;

Sequence=CAD12455.1; Type=Frameshift; Positions=17036, 17043;

6/30 PDB 3D structures from and Proteopedia for TTN (see all 30):

1BPV (3D)

1G1C (3D)

1NCT (3D)

1NCU (3D)

1TIT (3D)

1TIU (3D)

Secondary accessions: A6NKB1 E7EQE6 E7ET18 K7ENY1 Q10465 Q10466 Q15598 Q2XUS3 Q32Q60 Q4U1Z6 Q4ZG20

Q6NSG0 Q6PDB1 Q6PJP0 Q7KYM2 Q7KYN4 Q7KYN5 Q7LDM3 Q7Z2X3 Q8TCG8 Q8WZ51 Q8WZ52 Q8WZ53 Q8WZB3 Q92761

Q92762 Q9UD97 Q9UP84 Q9Y6L9

Alternative splicing: 12 isoforms: Q8WZ42-1 Q8WZ42-2 Q8WZ42-3 Q8WZ42-4 Q8WZ42-5 Q8WZ42-6 Q8WZ42-7 Q8WZ42-8

Q8WZ42-9 Q8WZ42-10 Q8WZ42-11 Q8WZ42-12 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for TTN: NX_Q8WZ42

Post-translational modifications:

Autophosphorylated (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q8WZ42

TTN Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (7 alternative transcripts):

NP_001243779.1 NP_001254479.1 NP_003310.4 NP_596869.4 NP_596870.2 NP_597676.3 NP_597681.3

ENSEMBL proteins:

ENSP00000343764 ENSP00000434586 ENSP00000467141 ENSP00000465570 ENSP00000401501

ENSP00000392336 ENSP00000408004 ENSP00000396805 ENSP00000399176 ENSP00000354117

ENSP00000405517 ENSP00000394672 ENSP00000340554 ENSP00000352154

Reactome Protein details: Q8WZ42
Human Recombinant Protein Products:

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	Novus Biologicals TTN Proteins
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for TTN

Gene Ontology (GO): 5/13 cellular component terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000794	condensed nuclear chromosome	IDA	9548712
GO:0005576	extracellular region	TAS	--
GO:0005634	nucleus	IDA	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	IDA	--

TTN for ontologies About GeneDecksing

TTN Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TTN
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	Novus Biologicals TTN Antibodies
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	Uscn Antibodies for TTN
	ThermoFisher Antibodies for TTN

Assay Products for TTN:

	Browse Kits and Assays available from EMD Millipore
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	Uscn ELISAs and CLIAs for TTN

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TTN for domains About GeneDecksing

5/14 InterPro domains/families (see all 14):

IPR003598 Ig_sub2

IPR007110 Ig-like_dom

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR003599 Ig_sub

IPR003961 Fibronectin_type3

Graphical View of Domain Structure for InterPro Entry Q8WZ42

ProtoNet protein and cluster: Q8WZ42

2 Blocks protein families:

IPB003598 Immunoglobulin C-2 type

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42

Domain: ZIS1 and ZIS5 regions contain multiple SPXR consensus sites for ERK- and CDK-like protein kinases as well as

multiple SP motifs. ZIS1 could adopt a closed conformation which would block the TCAP-binding site

Domain: The PEVK region may serve as an entropic spring of a chain of structural folds and may also be an interaction

site to other myofilament proteins to form interfilament connectivity in the sarcomere

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family

Similarity: Contains 132 fibronectin type-III domains

Similarity: Contains 152 Ig-like (immunoglobulin-like) domains

Similarity: Contains 19 Kelch repeats

Similarity: Contains 1 protein kinase domain

Similarity: Contains 17 RCC1 repeats

Similarity: Contains 14 TPR repeats

Similarity: Contains 15 WD repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42

Function: Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the

level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the

sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility

properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation

during mitosis. Might link the lamina network to chromatin or nuclear actin, or both during interphase

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme regulation: Full activation of the protein kinase domain requires both phosphorylation of Tyr-32341, preventing

it from blocking the catalytic aspartate residue, and binding of Ca/CALM to the C-terminal regulatory tail of the

molecule which results in ATP binding to the kinase

Genatlas biochemistry entry for TTN:

titin,giant sarcomeric protein,extending from the M line to the Z line of striated muscle sarcomere,essential in the

temporal and spatial control of the assembly of the highly ordered sarcomeres of striated muscles,responsible for the

elasticity of relaxed striated muscle

Enzyme Number (IUBMB): EC 2.7.11.1¹

miRNA Products:		OriGene 3'-UTR Clone (see all 5): TTN Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TTN
		8/18 QIAGEN miScript miRNA Assays for microRNAs that regulate TTN (see all 18):
		hsa-miR-522 hsa-miR-451 hsa-miR-1304 hsa-miR-144 hsa-miR-629* hsa-miR-1323 hsa-miR-532-5p hsa-miR-520g

		SwitchGear 3'UTR luciferase reporter plasmid: TTN 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TTN

Gene Ontology (GO): 5/17 molecular function terms (GO ID links to tree view) (see all 17): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002020	protease binding	IPI	9642272
GO:0003676	nucleic acid binding	IEA	--
GO:0004674	protein serine/threonine kinase activity	IDA	9804419
GO:0004713	protein tyrosine kinase activity	IEA	--
GO:0005509	calcium ion binding	IDA	7607248

TTN for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for TTN:

Decreased substrate adherent c

Increased cell death HMECs cel

Animal Models:
Mouse knock-outs for TTN: Ttn^tm1.1Her Ttn^tm1Mgot
13 MGI mutant phenotypes (inferred from 9 alleles) (MGI details for Ttn):

behavior/neurological	cardiovascular system	cellular	craniofacial	embryogenesis
growth/size	homeostasis/metabolism	immune system	mortality/aging	muscle
normal	skeleton	vision/eye

TTN for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Striated Muscle Contraction

	Striated Muscle Contraction	1.00			Muscle contraction	0.65
	Striated Muscle Contraction	0.87

Platelet degranulation

Platelet degranulation

1.00

Response to elevated platelet cytosolic Ca2+

0.94

Hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (HCM)

1.00

Dilated cardiomyopathy

0.75

Platelet activation, signaling and aggregation

Platelet activation, signaling and aggregation

1.00

Hemostasis

0.43

Pathway sources
See GeneCards unified pathways
Show all pathways

1 BioSystems Pathway for TTN

Striated Muscle Contraction

5/6 Reactome Pathways for TTN (see all 6)

	Hemostasis
	Muscle contraction
	Platelet degranulation
	Platelet activation, signaling and aggregation
	Response to elevated platelet cytosolic Ca2+

2 Kegg Pathways (Kegg details for TTN):

	Hypertrophic cardiomyopathy (HCM)
	Dilated cardiomyopathy

TTN for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TTN

5/125 Interacting proteins for TTN (Q8WZ42^{1, 2, 3}) via UniProtKB, MINT, STRING, and/or I2D (see all 125)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
OBSCN	Q5VST9¹^,²^,³	EBI-3448943,EBI-941850 MINT-7979881 MINT-7979650 MINT-7979863 MINT-7979665 MINT-7979826 MINT-7979808 MINT-7979844 I2D: score=3
ACTN2	P35609¹^,²^,³	EBI-3448943,EBI-928705 MINT-2882567 MINT-7899812 I2D: score=2
CAPN3	P20807¹^,²^,³	EBI-3448943,EBI-5655000 MINT-7990374 I2D: score=3
OBSL1	O75147²^,³	MINT-7979729 MINT-7979611 MINT-7979766 MINT-7979747 MINT-7979789 MINT-7979631 MINT-7979704 MINT-7979686 I2D: score=1
NEB	P20929²^,³	MINT-2882539 MINT-7032264 MINT-2882627 MINT-2882669 MINT-7032305 MINT-7032278 I2D: score=2

About this table

Gene Ontology (GO): 5/27 biological process terms (GO ID links to tree view) (see all 27): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001701	in utero embryonic development	IEA	--
GO:0001756	somitogenesis	--	--
GO:0002576	platelet degranulation	TAS	--
GO:0003007	heart morphogenesis	--	--
GO:0003300	cardiac muscle hypertrophy	IMP	11846417

TTN for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TTN for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TTN

1 HMDB Compound for TTN About this table

Compound	Synonyms	CAS #	PubMed Ids
Magnesium	Magnesium (see all 2)	7439-95-4	--

10/24 Novoseek chemical compound relationships for TTN gene (see all 24) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
ryanodine	54.5	27	11074791 (4), 9546812 (2), 14592894 (2), 16637922 (2) (see all 19)
proline	43.5	9	8760502 (1), 16339921 (1), 9675168 (1), 8937992 (1) (see all 8)
acetylcholine	40.5	12	9521611 (1), 9854961 (1), 14592910 (1), 16720217 (1) (see all 12)
actomyosin	40.1	8	12815860 (3), 16453158 (2), 8534821 (1)
leupeptin	37	3	11519738 (1), 9648223 (1), 8276755 (1)
valine	31.6	5	8760502 (1), 16339921 (1), 9675168 (1), 10364572 (1)
pip2	23.5	5	15833278 (1), 9657390 (1)
lysine	21.5	5	8760502 (1), 16339921 (1), 9675168 (1), 10364572 (1)
ethyl methanesulfonate	14.9	1	15259051 (1)
calcium	14.8	36	18690715 (6), 11519738 (4), 14706862 (3), 14593205 (1) (see all 18)

Search CenterWatch for drugs/clinical trials and news about TTN / TITIN

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TTN gene (7 alternative transcripts):

NM_001256850.1 NM_001267550.1 NM_003319.4 NM_133378.4 NM_133379.4 NM_133432.3 NM_133437.3

Unigene Cluster for TTN:

Titin

Hs.134602 [show with all ESTs]

Unigene Representative Sequence: NM_001267550

15 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000342992(uc002umw.1 uc002una.1 uc010frf.1 uc010fre.1 uc002umz.1 uc021vsy.1)

ENST00000460472(uc002umq.3 uc021vtb.1) ENST00000589042 ENST00000591111

ENST00000414766 ENST00000426232 ENST00000446966(uc002umx.1) ENST00000425332(uc010zfk.1)

ENST00000448510 ENST00000360870(uc010frg.1 uc002unb.2) ENST00000436599

ENST00000470257(uc002und.3) ENST00000412264 ENST00000342175(uc021vsz.1)

ENST00000359218(uc021vta.1)

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Additional cDNA sequence:

AF321609.2 AF525413.1 AK056602.1 AK090903.1 AK091732.1 AK092284.1 AK096883.1 AK125056.1

AK129531.1 AK129757.1 AK129919.1 AL713647.1 AL832094.1 AL832351.1 AL833110.1 AL833292.1

BC013396.2 BC017983.1 BC026297.1 BC029400.1 BC030823.1 BC058824.1 BC070170.1 BC107797.1

BX537998.1 DQ248309.1 EF212153.1 EF212154.1 EF212155.1 EF212156.1 EU428784.1 X64697.1

X64698.1 X69490.1 X83270.1 X90568.1 X90569.1 X98114.1 X98115.1

24/59 DOTS entries (see all 59):

DT.40305982 DT.87017845 DT.91943853 DT.102839578 DT.75106611 DT.100042202 DT.120958407 DT.120958414

DT.91775084 DT.120958266 DT.95208755 DT.100664174 DT.75136394 DT.120958289 DT.120958437 DT.220534

DT.95152671 DT.100042738 DT.100651430 DT.100913562 DT.101985634 DT.411096 DT.432606 DT.100642525

24/481 AceView cDNA sequences (see all 481):

AI803531 F36665 AI332429 AI269724 BX507270 BX501046 X83270 BX500025

BX501304 BQ926050 AA086447 CF552750 BX953355 F28302 BU743014 BX096752

F34840 BC058824 AI051675 AJ710712 AI338273 F16872 CF552550 F27402

GeneLoc Exon Structure

5/38 Alternative Splicing Database (ASD) splice patterns (SP) for TTN (see all 38) About this scheme

ExUns:	1a	·	1b	^	2	^	3	^	4	^	5	^	6a	·	6b	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17	^	18	^	19	^	20	^	21	^	22a	·	22b	^	23a	·
SP1:
SP2:
SP3:
SP4:
SP5:

ExUns:	23b	·	23c	^	24a	·	24b	^	25a	·	25b	^	26	^	27	^	28a	·	28b	^	29	^	30	^	31	^	32	^	33	^	34	^	35	^	36	^	37	^	38	^	39	^	40	^	41	^	42	^	43	^	44	^
SP1:
SP2:
SP3:
SP4:
SP5:

ExUns:	45	^	46	^	47	^	48	^	49	^	50	^	51	^	52	^	53	^	54	^	55	^	56	^	57	^	58	^	59a	·	59b	^	60a	·	60b	^	61	^	62	^	63	^	64a	·	64b	^	65	^	66	^	67	^
SP1:
SP2:
SP3:
SP4:
SP5:

ExUns:	68	^	69	^	70	^	71	^	72	^	73	^	74	^	75	^	76	^	77	^	78	^	79	^	80	^	81	^	82	^	83a	·	83b	^	84	^	85	^	86	^	87	^	88	^	89	^	90	^	91	^	92	^
SP1:																																			-		-		-		-
SP2:
SP3:
SP4:
SP5:

ExUns:	93	^	94a	·	94b	^	95	^	96a	·	96b	·	96c	^	97	^	98	^	99	^	100	^	101	^	102	^	103	^	104	^	105	^	106	^	107	^	108	^	109	^	110	^	111	^	112	^	113	^	114	^	115	^
SP1:							-
SP2:
SP3:
SP4:
SP5:

ExUns:	116	^	117	^	118	^	119	^	120	^	121	^	122	^	123	^	124	^	125	^	126	^	127	^	128	^	129	^	130	^	131a	·	131b	^	132a	·	132b	^	133	^	134	^	135	^	136	^	137	^	138	^	139	^
SP1:
SP2:
SP3:
SP4:
SP5:

ExUns:	140	^	141a	·	141b	^	142	^	143	^	144	^	145	^	146	^	147	^	148	^	149	^	150a	·	150b	^	151a	·	151b	·	151c	^	152a	·	152b	^	153a	·	153b	^	154	^	155	^	156	^	157	^	158	^	159	^
SP1:
SP2:
SP3:
SP4:
SP5:

ExUns:	160	^	161	^	162	^	163	^	164	^	165	^	166	^	167	^	168	^	169	^	170	^	171	^	172	^	173	^	174	^	175	^	176	^	177	^	178	^	179a	·
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for TTN

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TTN expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CAAGTATAAA

About this image

TTN expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10/24 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 24)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Myocardium

Forelimb Dorsal Muscles

Multinuclear Myocytes

Skeletal Muscle

Limb

Forelimb Ventral Muscles

Multinuclear Myocytes

Skeletal Muscle

Limb

Hindlimb Dorsal Muscle

Multinuclear Myocytes

Skeletal Muscle

Limb

Hindlimb Ventral Muscle

Multinuclear Myocytes

Skeletal Muscle

Anterior Neck Muscles

Multinuclear Myocytes

Skeletal Muscle

Cervical Back Muscles

Multinuclear Myocytes

Skeletal Muscle

Lumbar Back Muscles

Multinuclear Myocytes

Skeletal Muscle

Lumbar Vertebrae Column Muscles

Multinuclear Myocytes

Skeletal Muscle

Pelvic Muscles

Multinuclear Myocytes

Skeletal Muscle

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

Pancreatic endoderm/endocrine precursor-like cells (A scalable, suspensi...)

Cardiomyocyte-like progenitor cells (Derivation of cardio...)

See TTN Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TTN

SOURCE GeneReport for Unigene cluster: Hs.134602

UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42

Tissue specificity: Isoforms 3, 7 and 8 are expressed in cardiac muscle. Isoform 4 is expressed in vertebrate skeletal

muscle. Isoform 6 is expressed in skeletal muscle (at protein level)

SABiosciences Expression via Pathway-Focused PCR Arrays including TTN:

Interferons & Receptors in human mouse rat

Oxidative Stress in human mouse rat

Nitric Oxide Signaling Pathway in human mouse rat

Skeletal Muscle: Myogenesis & Myopathy in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for TTN gene from 5/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TTN¹	titin	74.67(n) 77.68(a)		424126 XM_421979.3 XP_421979.3
lizard (Anolis carolinensis)	Reptilia	TTN⁶	--	76(a)	1 ↔ 1	GL343320.1(716205-944482)
African clawed frog (Xenopus laevis)	Amphibia	48053412²	--	76.61(n)		48053412
zebrafish (Danio rerio)	Actinopterygii	AY081167.1²	--	78.18(n)		317731 AY081167.1
worm (Caenorhabditis elegans)	Secernentea	F21C10.7³	--	40(a) (best of 3)		V(9115384-9124640) --

ENSEMBL Gene Tree for TTN (if available)
TreeFam Gene Tree for TTN (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TTN gene

STK17B² DAPK2² MYLK2² MYLK3² STK17A² OBSCN² DAPK3² SPEG²

MYLK4² DAPK1² MYLK² OBSL1²

18/52 SIMAP similar genes for TTN using alignment to 13 protein entries: TITIN_HUMAN (see all proteins) (see all similar genes):

MYLK4 ROBO1 STK17B BRSK2 DAPK3 STK17A

CAMK2A DAPK1 PRKD1 MYLK DAPK2 RPS6KA1

PALLD CAMK4 PRKCH DKFZp686I10125 FGFR3 PHKG2

TTN for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for TTN
PGOHUM00000240442

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs267607156^1,2	C	pathogenic	179391848(-)	`AACCCC/TGATCA`	14	P L	mis¹ int¹		0	--	--	--	--
rs147879266^1,2	C,	pathogenic	179602841(+)	`TGACAC/TTGCCA`	12	N S	mis¹		0	--	--	--	--
rs267607158^1,2	C	pathogenic	179604852(-)	`AAGTGC/TAGGAG`	11	Q *	stg¹ int¹		0	--	--	--	--
rs267607155^1,2	C	pathogenic	179647707(-)	`TGACAA/C/TGGTAC`	21	R W	mis¹		0	--	--	--	--
rs267607157^1,2	C	pathogenic	179650717(-)	`TTCCGC/TCGCAA`	14	A V	mis¹		0	--	--	--	--
rs28933405^1,2	C	pathogenic	179650726(-)	`GGAACG/TCATTT`	14	R L	mis¹		0	--	--	--	--
rs138060032^1,2	C,F	pathogenic	179664293(+)	`CTGCCG/AAGCCA`	14	/R /W	mis¹		2		NA EU	5875
rs139517732^1,2	C,	pathogenic	179667000(+)	`CTGCAC/TGCCGG`	14	M V	mis¹		0	--	--	--	--
rs146359866^1,2	C	other	179611813(+)	`AATATC/TGCTCT`	8	Q R	int¹ mis¹		1		NA	4272
rs150820403^1,2	C	other	179615320(+)	`GTTTTC/TGAAAA`	8	Q R	int¹ mis¹		1		NA	3836

HapMap Linkage Disequilibrium report for TTN (179390716 - 179640716 bp, first 250kb of TTN)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 4 variations for TTN
4 CNVs: 32383 3400 4319 68206
Human Gene Mutation Database (HGMD): TTN

Locus Specific Mutation Databases (LSDB): TTN

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TTN

DNA2.0 Custom Variant and Variant Library Synthesis for TTN

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TTN for disorders           About GeneDecksing

OMIM gene information: 188840
OMIM disorders: 188840  604145  600334  608807  603689  611705
UniProtKB/Swiss-Prot: TITIN_HUMAN, Q8WZ42

Defects in TTN are the cause of hereditary myopathy with early respiratory failure (HMERF) [MIM:603689]; also

known as Edstrom myopathy. HMERF is an autosomal dominant, adult-onset myopathy with early respiratory muscle

involvement

Defects in TTN are the cause of familial hypertrophic cardiomyopathy type 9 (CMH9) [MIM:613765]. Familial

hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually

asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse,

palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial

variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death

Defects in TTN are the cause of cardiomyopathy dilated type 1G (CMD1G) [MIM:604145]. Dilated cardiomyopathy is

a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure

and arrhythmia. Patients are at risk of premature death

Defects in TTN are the cause of tardive tibial muscular dystrophy (TMD) [MIM:600334]; also known as Udd

myopathy. TMD is an autosomal dominant, late-onset distal myopathy. Muscle weakness and atrophy are usually confined

to the anterior compartment of the lower leg, in particular the tibialis anterior muscle. Clinical symptoms usually

occur at age 35-45 years or much later

Defects in TTN are the cause of limb-girdle muscular dystrophy type 2J (LGMD2J) [MIM:608807]. LGMD2J is an

autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle

muscles. Severe disability is observed within 20 years of onset

Defects in TTN are the cause of early-onset myopathy with fatal cardiomyopathy (EOMFC) [MIM:611705].

Early-onset myopathies are inherited muscle disorders that manifest typically from birth or infancy with hypotonia,

muscle weakness, and delayed motor development. EOMFC is a titinopathy that, in contrast with the previously described

examples, involves both heart and skeletal muscle, has a congenital onset, and is purely recessive. This phenotype is

due to homozygous out-of-frame TTN deletions, which lead to a total absence of titin's C-terminal end from striated

muscles and to secondary CAPN3 depletion

20/49 diseases for TTN (see all 49): About MalaCards

cardiomyopathy, dilated, 1g cardiomyopathy familial hypertrophic cardiomyopathy hypertrophic cardiomyopathy

limb-girdle muscular dystrophy type 2j limb-girdle muscular dystrophy morvan's fibrillary chorea lambert-eaton myasthenic syndrome

cardiomyopathy, familial hypertrophic, 9 tibial muscular dystrophy muscular dystrophy rhabdomyosarcoma

alveolar soft part sarcoma newborn respiratory distress syndrome hereditary myopathy with early respiratory failure centronuclear myopathy

rippling muscle disease myasthenia gravis salih myopathy myopathy

10 diseases from the University of Copenhagen DISEASES database for TTN:

Myopathy Thymoma Neuropathy Newborn respiratory distress syndrome

Dilated cardiomyopathy Hypertrophic cardiomyopathy Familial hypertrophic cardiomyopathy Hypersensitivity reaction type II disease

Meconium aspiration syndrome Diastolic heart failure

10/41 Novoseek disease relationships for TTN gene (see all 41) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
lgmd2a	80.4	15	10987085 (2), 14959561 (1), 9642272 (1), 11294923 (1) (see all 7)
lgmd2g	78.1	6	14959561 (1), 15316618 (1), 12379311 (1)
myasthenia gravis	75.5	31	9467662 (3), 11766610 (2), 11063835 (2), 9065023 (2) (see all 24)
thymoma	73.5	59	9451594 (4), 10896269 (4), 11182151 (4), 11706095 (4) (see all 23)
muscular dystrophy limb-girdle	72.8	4	16115818 (1), 8537379 (1), 18477606 (1), 15043707 (1)
lgmd1a	68.8	2	15316618 (1)
distal myopathies	67.9	5	17337483 (2), 15728284 (1), 16793270 (1), 18948003 (1)
lgmd2h	67.3	4	14959561 (1), 15316618 (1)
muscular dystrophies	64.7	19	11829483 (3), 16115818 (2), 11294923 (1), 8064303 (1) (see all 12)
lgmd2f	64.6	4	14959561 (1), 15316618 (1)

GeneTests: TTN

Familial Hypertrophic Cardiomyopathy

Dilated Cardiomyopathy

Udd Distal Myopathy

Human Genome Epidemiology (HuGE) Navigator: TTN (9 documents)

Export disorders for TTN gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TTN gene, integrated from 9 sources (see all 477):
(articles sorted by number of sources associating them with TTN)

Utopia: connect your pdf to the dynamic
world of online information

Familial dilated cardiomyopathy locus maps to chromosome 2q31. (PubMed id 10051295)^{1, 2, 3} Siu B.L.... Seidman C.E. (1999)
Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy. (PubMed id 16465475)^{1, 2, 9} Matsumoto Y.... Kimura A. (2005)
Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. (PubMed id 12145747)^{1, 2, 9} Hackman P.... Udd B. (2002)
Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. (PubMed id 11788824)^{1, 2, 9} Gerull B.... Thierfelder L. (2002)
Titin mutations as the molecular basis for dilated cardiomyopathy. (PubMed id 11846417)^{1, 2, 9} Itoh-Satoh M.... Kimura A. (2002)
Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity. (PubMed id 10850961)^{1, 2, 9} Freiburg A.... Labeit S. (2000)
Association of the chaperone alphaB-crystallin with titin in heart muscle. (PubMed id 14676215)^{1, 2, 9} Bullard B.... Linke W.A. (2004)
Structural evidence for a possible role of reversible disulphide bridge formation in the elasticity of the muscle protein titin. (PubMed id 11525170)^{1, 2, 9} Mayans O.... Wilmanns M. (2001)
The three-dimensional structure of a type I module from titin: a prototype of intracellular fibronectin type III domains. (PubMed id 9782056)^{1, 2, 9} Goll C.M.... Nilges M. (1998)
Titins, giant proteins in charge of muscle ultrastructure and elasticity. (PubMed id 7569978)^{1, 2, 9} Labeit S. and Kolmerer B. (1995)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 7273	HGNC: 12403	AceView: TTN	Ensembl:ENSG00000155657	euGenes: HUgn7273
ECgene: TTN	Kegg: 7273	H-InvDB: TTN

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TTN	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TTN	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TTN
Wikipedia	http://en.wikipedia.org/wiki/Titin

Intellectual Property for TTN gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TTN gene:
Search GeneIP for patents involving TTN

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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TTN Gene

titin

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Limb girdle
LGMD2I
Neurological Disorders
Centronuclear myopathy
Retinoblastoma
MYOPATHY, CONGENITAL
Familial Hypertrophic Cardiomyopathy
Muscular Dystrophies
LGMD2G
Thymoma
Udd Distal Myopathy
Distal Myopathies
epithelial tumor
LGMD2E
Ischemia
LGMD2F
Myasthenia Gravis
Ventricular Dysfunction Left
Myopathy
Neuromuscular Diseases
Rhabdomyosarcoma
Respiratory failure
HEART FAILURE
Cardiomyopathy
LGMD2B
Shock
Heart Diseases
LGMD2A
Muscular Dystrophy Duchenne
Autoimmune Response
Hypertrophy
Atrophy
Muscular Dystrophy Limb-Girdle
Pulmonary Disease Chronic Obstructive
Tumors
Myositis
Necrosis
Autoimmunity
mimicry
Dilated Cardiomyopathy
Polymyositis
LGMD1A
LGMD2H

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TTN Gene

titin

Aliasesfor TTN gene

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Proteinsfor TTN gene

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Functionfor TTN gene

Pathways & Interactionsfor TTN gene

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Specialized Databases showing TTN gene

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Aliases
for TTN gene

Summaries
for TTN gene

Genomic Views
for TTN gene

Proteins
for TTN gene

Protein Domains /
Families
for TTN gene

Function
for TTN gene

Pathways & Interactions
for TTN gene

Drugs & Compounds
for TTN gene

Transcripts
for TTN gene

Expression
for TTN gene

Orthologs
for TTN gene

Paralogs
for TTN gene

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for TTN gene

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for TTN gene

Publications
for TTN gene

Intellectual Property
for TTN gene

Products
for TTN gene