Congenital myopathy

Gene: TPM2

Green List (high evidence)

TPM2 (tropomyosin 2)
EnsemblGeneIds (GRCh38): ENSG00000198467
EnsemblGeneIds (GRCh37): ENSG00000198467
OMIM: 190990, Gene2Phenotype
TPM2 is in 7 panels

6 reviews

Ivone Leong (Genomics England Curator)

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 cases
Created: 12 Jul 2021, 9:50 a.m. | Last Modified: 12 Jul 2021, 9:50 a.m.
Panel Version: 2.53

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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

Louise Daugherty (Genomics England Curator)

I don't know

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.

Rachael Mein (Viapath at Guy's Hospital)

Green List (high evidence)

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

Anna Sarkozy (Great Ormond Street Hospital)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Comment when marking as ready: Many families, monoallelic except single case with pterygia
Created: 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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • London South GLH
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Emory Genetics Laboratory
Phenotypes
  • CAP myopathy 2, OMIM:609285
  • Nemaline myopathy 4, autosomal dominant, OMIM:609285
  • Congenital myopathy, MONDO:0019952
  • Multiple pterygium syndrome, MONDO:0017415
OMIM
190990
Clinvar variants
Variants in TPM2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Jul 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

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

12 Jul 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

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

12 Jul 2021, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: TPM2 were set to 12592607; 11738357; 17434307; 24692096; 32092148; 27726070

12 Jul 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

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

8 Jul 2021, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: TPM2 were set to 12592607; 11738357; 17434307; 24692096

3 May 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TPM2 were set to

3 May 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

30 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TPM2.

30 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source London South GLH was added to TPM2. Rating Changed from Green List (high evidence) to Green List (high evidence)

22 Feb 2017, Gel status: 4

panel promoted to version 1

Helen Brittain (Genomics England Curator)

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.

2 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

2 Feb 2017, Gel status: 4

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for TPM2 were set to CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285

2 Feb 2017, Gel status: 4

Set Mode of Inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for TPM2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 May 2015, Gel status: 4

Added New Source

Eik Haraldsdottir (Genomics England)

TPM2 was added to Congenital myopathypanel. Sources: Expert

28 Apr 2015, Gel status: 4

Added New Source

GEL ()

TPM2 was added to Congenital myopathypanel. Sources: Radboud University Medical Center, Nijmegen

28 Apr 2015, Gel status: 3

Added New Source

GEL ()

TPM2 was added to Congenital myopathypanel. Sources: Illumina TruGenome Clinical Sequencing Services

28 Apr 2015, Gel status: 2

Added New Source

GEL ()

TPM2 was added to Congenital myopathypanel. Sources: UKGTN

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

TPM2 was added to Congenital myopathypanel. Sources: Emory Genetics Laboratory