Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
Gene: TTNThe recent MOI update on this panel was done following an audit of genes with different MOIs on component panels of the same superpanel. These were reviewed by the curation team accounting for respective panel scope and final MOIs were validated by the Genomics England clinical team.Created: 3 Aug 2022, 3:30 p.m. | Last Modified: 3 Aug 2022, 3:30 p.m.
Panel Version: 2.44
The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 12:04 p.m. | Last Modified: 9 Mar 2022, 12:04 p.m.
Panel Version: 2.37
Comment on list classification: Promoted from Red to Green due to overall the majority of reviews are Green, and there is a consensus that although classifying variants in this is difficult, additional phenotyping studies can aid in confirmation of diagnosis and that this gene should be included on this panel.Created: 28 Nov 2019, 3:28 p.m. | Last Modified: 28 Nov 2019, 3:28 p.m.
Panel Version: 1.102
Disese spectrum can be very variable from congenital myopathy, cardiomyopathy, distal weakness, HMERF to LGMD. Known form of LGMD2J or LGMDR10Created: 21 Oct 2019, 1:27 p.m. | Last Modified: 21 Oct 2019, 1:27 p.m.
Panel Version: 1.97
Loss of function variants and missense variants are also reported as pathogenic. The analysis of titin variants is more complex than this proforma allows forCreated: 10 May 2019, 2:15 p.m.
Phenotypes
Limb-girdle muscular dystrophy; distal myopathy; HMERF; dilated cardiomyopathy; arthrogryposis; myofibrillar myopathy
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Review and rating from Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 30 Apr 2019, 11:45 a.m.
Complex phenotype, unlikely pure LGMD. Paper describes variety. PMIDL12145747 - large Finnish family with LGMD2J. Identified homozygosity for an 11-bp deletion/insertion in the last exon (exon 363). Family members affected with the milder adult-onset TMD phenotype were heterozygous for the TTN deletion.Created: 30 Apr 2019, 11:24 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Muscular dystrophy, limb-girdle, type 2J, 608807
Publications
Currently only recurrent HMERF associated mutations are reported by this lab but truncating variants are also of great clinical interest. Difficulty classifying variants in titin should not be a reason not to include this gene as additional phenotyping studies such as muscle MRI, biopsy review and protein analysis is often extremely helpful in confirming or refuting the diagnosis.Created: 29 Mar 2019, 1:14 p.m.
Loss of function variants are simpler to classify but missense variants are also reported as pathogenic. The analysis of titin variants is more complex than this proforma allows forCreated: 26 Mar 2019, 4:54 p.m.
Phenotypes
Limb girdle muscular dystrophy; Distal myopathy; Myofibrillar myopathy; Congenital myopathy; dilated cardiomyopathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Listed as associated with Limb Girdle Muscular Dystrophy by Gene Advisor (June 2016), Steve AbbsCreated: 27 Jul 2016, 8:27 a.m.
Comment on phenotypes: Also associated with Cardiomyopathy, dilated, 1G 604145; Cardiomyopathy, familial hypertrophic, 9 613765; Myopathy, early-onset, with fatal cardiomyopathy 611705; Myopathy, proximal, with early respiratory muscle involvement 603689; Tibial muscular dystrophy, tardive 600334Created: 26 Jul 2016, 1:52 p.m.
Comment when marking as ready: Associated with phenotype in OMIM, not G2P (for this phenotype). Found in 3/4 sources. One reviewer recommends Amber. Three variants reported one each in Finnish, French and Han Chinese families (26392295; 12145747), not very strong evidence for the pathogenicity of these variants.
Comment from Emma Clement: Predominantly myopathy gene (in terms of muscle phenotype) really but I think lots of mutations in this will have been missed as it it not screened due to size. I think you could leave this orange for nowCreated: 14 Jun 2016, 10:26 a.m.
Comment on list classification: A particular homozygous 11bp deletion has been found in a small number of patients with LGMD. Many other muscle phenotypes plus cardiomyopathy associated with monoallelic and biallelic mutations in this highly polymorphic gene.Created: 29 May 2016, 2:51 p.m.
Mode of inheritance for gene TTN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity for gene: TTN was changed from to Other
Gene: ttn has been classified as Green List (High Evidence).
Source Yorkshire and North East GLH was added to TTN.
Phenotypes for gene: TTN were changed from Muscular dystrophy, limb-girdle, type 2J, 608807; Limb girdle muscular dystrophy; Distal myopathy; Myofibrillar myopathy; Congenital myopathy; dilated cardiomyopathy to Muscular dystrophy, limb-girdle, type 2J, 608807; Limb girdle muscular dystrophy; Distal myopathy; Myofibrillar myopathy; Congenital myopathy; dilated cardiomyopathy; HMERF; arthrogryposis
Phenotypes for gene: TTN were changed from Muscular dystrophy, limb-girdle, type 2J 608807 to Muscular dystrophy, limb-girdle, type 2J, 608807; Limb girdle muscular dystrophy; Distal myopathy; Myofibrillar myopathy; Congenital myopathy; dilated cardiomyopathy
Publications for gene: TTN were set to 26392295; 12145747
Source NHS GMS was added to TTN.
Source South West GLH was added to TTN.
Comments from Fiona Karet included. A Green review for each gene relevant for this panel on the Gene Advisor download has been included.
This gene has been classified as Red List (Low Evidence).
Phenotypes for TTN were set to Muscular dystrophy, limb-girdle, type 2J 608807
Phenotypes for TTN were set to Tibial muscular dystrophy, tardive, 600334
This gene has been classified as Amber List (Moderate Evidence).
Phenotypes for TTN were set to Cardiomyopathy, dilated, 1G, 604145; Cardiomyopathy, familial hypertrophic, 9, 613765; Muscular dystrophy, limb-girdle, type 2J 608807; Myopathy, early-onset, with fatal cardiomyopathy, 611705; Myopathy, proximal, with early respiratory muscle involvement, 603689; Tibial muscular dystrophy, tardive, 600334
Publications for TTN were set to 26392295; 12145747
This gene has been classified as Amber List (Moderate Evidence).
Model of inheritance for gene TTN was changed to BIALLELIC, autosomal or pseudoautosomal
TTN was added to Limb girdle muscular dystrophypanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
Model of inheritance for gene TTN was changed to BIALLELIC, autosomal or pseudoautosomal
TTN was added to Limb girdle muscular dystrophypanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
TTN was added to Limb girdle muscular dystrophypanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen