TTN
Homo sapiens
Gene Name: titin
Aliases: CMD1G, CMH9, CMPD4
Chromosome No: 2
Chromosome Band: 2q31.2
Genetic Category: Rare Single Gene variant-Syndromic
Aliases: CMD1G, CMH9, CMPD4
Chromosome No: 2
Chromosome Band: 2q31.2
Genetic Category: Rare Single Gene variant-Syndromic
Summary Statistics:
ASD Reports: 33
Recent Reports: 4
Annotated variants: 164
Associated CNVs: 8
Evidence score: 4
ASD Reports: 33
Recent Reports: 4
Annotated variants: 164
Associated CNVs: 8
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
Rare mutations in the TTN gene have been identified with autism (O'Roak et al., 2011 & 2012).
Molecular Function
Key component in the assembly and functioning of vertebrate striated muscles. Contributes to fine balance of forces between two halves of the sarcomere.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.
ASD
Positive Association
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Tourette syndrome
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Support
De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.
OCD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Diagnostic exome sequencing in persons with severe intellectual disability.
ID
Epilepsy, ASD
Support
Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.
ASD
Support
Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants
ASD
ADHD, DD, ID
Support
Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.
ASD
Support
A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders
ASD, epilepsy/seizures
DD, ID
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.
ASD
Support
Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolesce...
ASD
Highly Cited
Reversible unfolding of individual titin immunoglobulin domains by AFM.
Highly Cited
Elasticity and unfolding of single molecules of the giant muscle protein titin.
Highly Cited
Folding-unfolding transitions in single titin molecules characterized with laser tweezers.
Recent Recommendation
Germline TTN variants are enriched in PTEN-wildtype Bannayan-Riley-Ruvalcaba syndrome.
Bannayan-Riley-Ruvalcaba syndrome (BRRS)
ASD/DD
Recent Recommendation
De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.
Recent Recommendation
Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3.
Recent Recommendation
Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN260R006a
missense_variant
c.98224G>C
p.Gly32742Arg
Familial
Paternal
Simplex
GEN260R006b
missense_variant
c.48137G>T
p.Gly16046Val
Familial
Maternal
Simplex
GEN260R007
missense_variant
c.107723T>C
p.Ile35908Thr
De novo
Unknown
GEN260R008
missense_variant
c.78590C>T
p.Pro26197Leu
De novo
Unknown
GEN260R009
splice_site_variant
c.46513+1G>A
De novo
Unknown
GEN260R010
missense_variant
c.18943G>A
p.Val6315Met
De novo
Unknown
GEN260R011
missense_variant
c.18550G>A
p.Ala6184Thr
De novo
Unknown
GEN260R012
missense_variant
c.10731G>C
p.Lys3577Asn
De novo
Unknown
GEN260R013
missense_variant
c.8651T>A
p.Ile2884Asn
De novo
Unknown
GEN260R026
missense_variant
c.17297G>C;c.17672G>C;c.17873G>C;c.36788G>C;c.39569G>C;c.44492G>C
p.Gly5766Ala;p.Gly5891Ala;p.Gly5958Ala;p.Gly12263Ala;p.Gly13190Ala;p.Gly14831Ala
De novo
Simplex
GEN260R027
missense_variant
c.23518C>T;c.23893C>T;c.24094C>T;c.43009C>T;c.45790C>T;c.50713C>T
p.Arg7840Cys;p.Arg7965Cys;p.Arg8032Cys;p.Arg14337Cys;p.Arg15264Cys;p.Arg16905Cys
De novo
Simplex
GEN260R028
missense_variant
c.17603G>A;c.17978G>A;c.18179G>A;c.G37094G>A;c.39875G>Ac.44798G>A
p.Cys5868Tyr;p.Cys5993Tyr;p.Cys6060Tyr;p.Cys12365Tyr;p.Cys13292Tyr;p.Cys14933Tyr
De novo
Simplex
GEN260R029
missense_variant
c.73472T>C;c.73847T>Cc.74048T>C;c.92963T>C;c.95744T>C;c.100667T>C
p.Ile24491Thr;p.Ile24616Thr;p.Ile24683Thr;p.Ile30988Thr;p.Ile31915Thr;p.Ile33556Thr
De novo
Simplex
GEN260R030
missense_variant
c.11707C>A
p.Pro3903Thr
Familial
Paternal
Simplex
GEN260R038
missense_variant
c.15286T>C
p.Cys5096Arg
Familial
Paternal
Multi-generational
GEN260R052
splice_site_variant
c.31145-3_31167del
Familial
Paternal
Multiplex
GEN260R065a
missense_variant
c.90617G>A
p.Arg30206His
Familial
Paternal
Simplex
GEN260R065b
missense_variant
c.53512C>T
p.Arg17838Cys
Familial
Paternal
Simplex
GEN260R065c
missense_variant
c.39653T>C
p.Leu13218Ser
Familial
Maternal
Simplex
GEN260R065d
missense_variant
c.20828C>A
p.Ser6943Tyr
Familial
Maternal
Simplex
GEN260R065e
missense_variant
c.16001C>T
p.Pro5334Leu
Familial
Maternal
Simplex
GEN260R066a
missense_variant
c.54684T>A
p.Phe18228Leu
Familial
Paternal
Simplex
GEN260R066b
missense_variant
c.33905G>A
p.Arg11302Gln
Familial
Paternal
Simplex
GEN260R066c
missense_variant
c.33742G>A
p.Val11248Ile
Familial
Paternal
Simplex
GEN260R066d
missense_variant
c.12178G>A
p.Ala4060Thr
Familial
Paternal
Simplex
GEN260R066e
missense_variant
c.11927C>T
p.Thr3976Met
Familial
Maternal
Simplex
GEN260R067a
missense_variant
c.46942G>A
p.Gly15648Arg
Familial
Paternal
Simplex
GEN260R067b
missense_variant
c.78308C>A
p.Ala26103Asp
Familial
Maternal
Simplex
GEN260R068a
missense_variant
c.24243T>A
p.Asp8081Glu
Familial
Paternal
Simplex
GEN260R068b
missense_variant
c.79760A>T
p.Glu26587Val
Familial
Maternal
Simplex
GEN260R068c
missense_variant
c.68422C>T
p.Arg22808Cys
Familial
Maternal
Simplex
GEN260R068d
missense_variant
c.38639C>T
p.Pro12880Leu
Familial
Maternal
Simplex
GEN260R068e
missense_variant
c.28733A>G
p.Lys9578Arg
Familial
Maternal
Simplex
GEN260R068f
missense_variant
c.31399C>G
p.Leu10467Val
Familial
Maternal
Simplex
GEN260R068g
missense_variant
c.20222G>A
p.Gly6741Asp
Familial
Maternal
Simplex
GEN260R069a
missense_variant
c.28997T>C
p.Val9666Ala
Familial
Paternal
Simplex
GEN260R069b
missense_variant
c.14327T>C
p.Leu4776Ser
Familial
Maternal
Simplex
GEN260R127
stop_gained
c.98159T>G
p.Leu32720Ter
Familial
Maternal
Multiplex
GEN260R132
frameshift_variant
c.103043_103044insA
p.Thr34349AspfsTer11
Familial
Paternal
Multiplex
Common
No Common Variants Available
