Congenital myopathy
Gene: TTN
Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.Created: 30 Apr 2019, 10:09 a.m.
Comment when marking as ready: Cause of congenital myopathy (preceding cardiomyopathy) in >4 families in association with recessive truncating mutationsCreated: 6 Feb 2017, 9:14 a.m.
Comment on phenotypes: This is the only phenotype considered appropriate for the congenital myopathy panel.Created: 6 Feb 2017, 9:13 a.m.
Comment on mode of inheritance: Although monoallelic mutations can cause disease (predominantly cardiomyopathy) for the purposes of this panel, the appropriate phenotype is described as being caused by recessive truncating mutations (See PMIDs)Created: 6 Feb 2017, 9:11 a.m.
Comment on list classification: 17444505 two families with recessive truncating mutations presenting with congenital / infantile myopathy. Subsequent onset of DCM in mid-childhood. 23975875 - five further individuals with recessive truncating mutations and (2/5) congenital onset myopathy.Created: 6 Feb 2017, 9:09 a.m.
Myopathy, early onset with fatal cardiomyopathy described in association with homozygous truncating mutations in two families. AD inheritance seen in proximal myopathy with respiratory muscle involvement, however this has a later age of onset (average 35 years), therefore probably not relevant to congenital myopathy. Also well known to have a large range of missense mutations without clear pathological implication.Created: 26 Jan 2017, 1:38 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Myopathy, early-onset, with fatal cardiomyopathy 611705; Myopathy, proximal, with early respiratory muscle involvement 603689
Publications
From Illumina information for this gene, Hereditary Myopathy with Early Respiratory Failure and Udd Distal Myopathy have a dominant mode of inheritance, whereas Salih Myopathy is recessive.Created: 2 Jul 2015, 2:44 p.m.
Phenotypes for gene: TTN were changed from Myopathy, early-onset, with fatal cardiomyopathy, 611705 to Salih myopathy, OMIM:611705
Phenotypes for gene: TTN were changed from Myopathy, early-onset, with fatal cardiomyopathy 611705 to Myopathy, early-onset, with fatal cardiomyopathy, 611705
Source NHS GMS was added to TTN.
Source London South GLH was added to TTN. Rating Changed from Green List (high evidence) to Green List (high evidence)
Publications for TTN were set to 17444505; 23975875;28295036
Promoted 22/02/2017 after curation discussion and further review with members of the Genomics England curation team. Participants who are offered this panel will automatically be offered the following three panels: 1) Congenital muscular dystrophy 2) Congenital myasthenia and 3) Paediatric motor neuronopathy as this will cover a large range of differentials for a weak infant, for where the strict inclusion criteria are not applicable in view of the availability of muscle biopsy testing in peripheral paediatric units.
This gene has been classified as Green List (High Evidence).
Phenotypes for TTN were set to Myopathy, early-onset, with fatal cardiomyopathy 611705
Publications for TTN were set to 17444505; 23975875
Mode of inheritance for TTN was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
TTN was added to Congenital myopathypanel. Sources: Expert
TTN was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen
TTN was added to Congenital myopathypanel. Sources: UKGTN
TTN was added to Congenital myopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services