Congenital myopathy
Gene: TPM2
Comment on mode of inheritance: Three unrelated cases are reported with biallelic variants in TPM2. This is sufficient evidence to update the MOI from "MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.Created: 4 Apr 2023, 12:39 p.m. | Last Modified: 4 Apr 2023, 12:40 p.m.
Panel Version: 4.24
PMID:19155175 reported the identification of a homozygous null variant in TPM2 gene in a patient presented with nemaline myopathy associated with a non-lethal multiple pterygium syndrome.
Among 28 patients from 27 families reported in PMID:24692096, only one patient presenting with nemaline myopathy and pterygia was identified with recessive TPM2 variant.
A homozygous intronic sequence variant was identified in the patient reported with Escobar variant of multiple pterygium syndrome and congenital myopathy in PMID:33558124.
Only phenotypes associated with monoallelic variants (and NOT biallelic variants) are currently reported in OMIM and in Gene2Phenotype.
Created: 4 Apr 2023, 9:58 a.m. | Last Modified: 4 Apr 2023, 12:38 p.m.
Panel Version: 4.23
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
As there are only currently 2 homozygous cases, there is currently not enough evidence to support a change in MOI. It should also be noted that the parents (heterozygous for the variants) were asymptomatic.Created: 12 Jul 2021, 10:43 a.m. | Last Modified: 12 Jul 2021, 10:43 a.m.
Panel Version: 2.55
Comment on publications: PMID: 19155175 and 33558124 describe the 2 homozygous casesCreated: 12 Jul 2021, 9:50 a.m. | Last Modified: 12 Jul 2021, 9:50 a.m.
Panel Version: 2.53
Note two families reported now with bi-allelic disease, one presenting with congenital myopathy and the other with multiple pterygium syndrome.Created: 13 Jun 2021, 7:58 a.m. | Last Modified: 13 Jun 2021, 7:58 a.m.
Panel Version: 2.28
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Congenital myopathy; Multiple pterygium syndrome
Publications
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.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120: Arthrogryposis, distal, type 2B 601680
Publications
Variants in this GENE are reported as part of current diagnostic practice
comment re inheritance: recessive TPM2 pathogenic variant has been described in a patient with multiple pterygium syndrome and congenital myopathy. heterozygous carrier parents were unaffected, supporting recessive inheritance of the variant.Created: 24 Mar 2023, 1:05 p.m. | Last Modified: 24 Mar 2023, 1:05 p.m.
Panel Version: 4.2
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy
Publications
Comment when marking as ready: Many families, monoallelic except single case with pterygiaCreated: 2 Feb 2017, 12:10 p.m.
Comment on mode of inheritance: One case of Nemaline myopathy and pterygia found with homozygous mutation. All heterozygous otherwise.Created: 2 Feb 2017, 12:09 p.m.
Note that the only cases I found of truncating mutations were in a homozygous form. Otherwise, dominant inheritance appears to be associated with missense mutations.Created: 26 Jan 2017, 1:12 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285
Publications
Tag Q2_23_NHS_review tag was added to gene: TPM2.
Tag Q2_23_MOI tag was added to gene: TPM2.
Mode of inheritance for gene: TPM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TPM2 were changed from CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Congenital myopathy, MONDO:0019952; Multiple pterygium syndrome, MONDO:0017415 to CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285
Tag watchlist_moi tag was added to gene: TPM2.
Phenotypes for gene: TPM2 were changed from CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Arthrogryposis multiplex congenita, distal, type1, OMIM:108120: Arthrogryposis, distal, type 2B, OMIM:601680; Congenital myopathy, MONDO:0019952; Multiple pterygium syndrome, MONDO:0017415 to CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Congenital myopathy, MONDO:0019952; Multiple pterygium syndrome, MONDO:0017415
Phenotypes for gene: TPM2 were changed from CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Arthrogryposis multiplex congenita, distal, type1, OMIM:108120: Arthrogryposis, distal, type 2B, OMIM:601680 to CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Arthrogryposis multiplex congenita, distal, type1, OMIM:108120: Arthrogryposis, distal, type 2B, OMIM:601680; Congenital myopathy, MONDO:0019952; Multiple pterygium syndrome, MONDO:0017415
Publications for gene: TPM2 were set to 12592607; 11738357; 17434307; 24692096; 32092148; 27726070
Phenotypes for gene: TPM2 were changed from CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120: Arthrogryposis, distal, type 2B 601680 to CAP myopathy 2, OMIM:609285; Nemaline myopathy 4, autosomal dominant, OMIM:609285; Arthrogryposis multiplex congenita, distal, type1, OMIM:108120: Arthrogryposis, distal, type 2B, OMIM:601680
Publications for gene: TPM2 were set to 12592607; 11738357; 17434307; 24692096
Publications for gene: TPM2 were set to
Phenotypes for gene: TPM2 were changed from CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285 to CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Arthrogryposis multiplex congenita, distal, type1 108120: Arthrogryposis, distal, type 2B 601680
Source NHS GMS was added to TPM2.
Source London South GLH was added to TPM2. Rating Changed from Green List (high evidence) to Green List (high evidence)
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 TPM2 were set to CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285
Mode of inheritance for TPM2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
TPM2 was added to Congenital myopathypanel. Sources: Expert
TPM2 was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen
TPM2 was added to Congenital myopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services
TPM2 was added to Congenital myopathypanel. Sources: UKGTN
TPM2 was added to Congenital myopathypanel. Sources: Emory Genetics Laboratory