Dilated cardiomyopathy - adult and teen

Gene: TTN

Green List (high evidence)

TTN (titin)
EnsemblGeneIds (GRCh38): ENSG00000155657
EnsemblGeneIds (GRCh37): ENSG00000155657
OMIM: 188840, Gene2Phenotype
TTN is in 18 panels

8 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 3 Dec 2019, 2:28 p.m. | Last Modified: 3 Dec 2019, 2:28 p.m.
Panel Version: 0.52

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

On CGGL Royal Brompton DCM panel. Multiple pathogenic variants reported in DCM cases. Very good evidence in literature. Definitive DCM gene - Truncating variants only, we consider missense variants currently uninterpretable
Created: 19 Sep 2019, 10:38 p.m. | Last Modified: 19 Sep 2019, 10:38 p.m.
Panel Version: 0.44

Publications

Variants in this GENE are reported as part of current diagnostic practice

Rebecca Whittington (South West GLH)

Green List (high evidence)

Cardiomyopathy, dilated, 1G OMIM#604145; Cardiomyopathy, familial hypertrophic, 9 OMIM#613765; Muscular dystrophy, limb-girdle, autosomal recessive 10 OMIM#608807; Myopathy, proximal, with early respiratory muscle involvement#603689; Salih myopathy OMIM#611705; Tibial muscular dystrophy, tardive OMIM#600334
Created: 25 Mar 2019, 4:30 p.m.
Included in review of DCM genes: Dalin 2017 International Journal of Cardiology 228 (2017) 742748, Hershberger 2013 Nat Rev Cardiol 10:531 (quoted as 25% of DCM patients) and Pugh (2014) Genet Med 16, 601. Also refer to Roberts (2015) Sci Transl Med 7: 270ra6.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

I don't know

Comment on list classification: This gene appears on 3/4 gene lists submitted from GLHs, and has consistent Green reviews.
Created: 24 Mar 2019, 10:28 a.m.
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 346 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no stated association with DCM, limited association with hypertrophic cardiomyopathy (accessed 29/01/2019).
Created: 15 Feb 2019, 8:56 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, dilated, 1G (604145); Cardiomyopathy, familial hypertrophic, 9 (613765); Muscular dystrophy, limb-girdle, autosomal recessive 10 (608807); Myopathy, proximal, with early respiratory muscle involvement (603689); Salih myopathy (611705); Tibial muscular dystrophy, tardive (600334)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Bill Newman (Manchester Centre for Genomic Medicine)

Red List (low evidence)

Caroline Wright (Genomics England Curator)

Comment when marking as ready: On Manchester diagnostic panel; ideally ignore missense variation
Created: 14 Feb 2016, 4:25 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Green List (high evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • UKGTN
  • South West GLH
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • London South GLH
  • North West GLH
  • Expert list
  • Emory Genetics Laboratory
  • South West GLH
  • London South GLH
  • North West GLH
Phenotypes
  • Myopathy, proximal, with early respiratory muscle involvement (603689)
  • Cardiomyopathy, familial hypertrophic, 9 (613765)
  • Tibial muscular dystrophy, tardive (600334)
  • Muscular dystrophy, limb-girdle, autosomal recessive 10 (608807)
  • Cardiomyopathy, dilated, 1G (604145)
  • Salih myopathy (611705)
  • Cardiomyopathy, dilated, 1G
OMIM
188840
Clinvar variants
Variants in TTN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Dec 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: TTN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

12 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: TTN were set to 20186049; 27532257

24 Mar 2019, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: ttn has been classified as Green List (High Evidence).

8 Mar 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: TTN was added gene: TTN was added to Dilated cardiomyopathy - adult and teen. Sources: Emory Genetics Laboratory,Expert list,North West GLH,Expert Review Green,London South GLH,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,South West GLH,UKGTN Mode of inheritance for gene: TTN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TTN were set to 20186049; 27532257 Phenotypes for gene: TTN were set to Myopathy, proximal, with early respiratory muscle involvement (603689); Cardiomyopathy, familial hypertrophic, 9 (613765); Tibial muscular dystrophy, tardive (600334); Muscular dystrophy, limb-girdle, autosomal recessive 10 (608807); Cardiomyopathy, dilated, 1G (604145); Salih myopathy (611705); Cardiomyopathy, dilated, 1G