Muscular dystrophy and myopathy_Paediatric

Gene: TPM3

Green List (high evidence)

TPM3 (tropomyosin 3)
EnsemblGeneIds (GRCh38): ENSG00000143549
EnsemblGeneIds (GRCh37): ENSG00000143549
OMIM: 191030, Gene2Phenotype
TPM3 is in 8 panels

2 reviews

Sangavi Sivagnanasundram (Melbourne Health)

Green List (high evidence)

Variable age of onset due to the variability of phenotypes. Mutations in TPM3 cause a diverse group of congenital myopathies all characterised by muscle weakness/hypotonia.

AD Congenital Myopathy:
PMID: 26418456
Quantitative in vitro motility assay show that gain of function is mechanism of disease - mutations in the TPM3 gene led to an increased function in the myofibres/muscle cells.
2 unrelated individuals with ΔE218 and ΔE224 de novo deletions in TPM3 with muscle stiffness. Both muscle biopsies showed features of mild myopathy.

PMID: 18300303
4 individuals with phenotypic features of congenital myopathy and mutation present in TPM3

AR Congenital myopathy:
PMID: 10619715
Individual from consanguineous parents with severe symptoms of congenital myopathy

PMID: 12196661
Individual who is a compound heterozygote for nemaline myopathy

PMID: 18382475
Affected individuals from two turkish families with myopathy phenotypes.
Sources: Other
Created: 9 May 2023, 4:21 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy 4A, autosomal dominant (MIM#255310); Congenital myopathy 4B, autosomal recessive (MIM#609284)

Publications

Mode of pathogenicity
Other

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterised by muscle weakness.

Note report of two individuals with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one PMID 26418456. GOF proposed.
Created: 16 Oct 2020, 8:53 a.m. | Last Modified: 16 Oct 2020, 8:53 a.m.
Panel Version: 0.291

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
CAP myopathy 1, MIM# 609284; Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284; Congenital muscle stiffness

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
Phenotypes
  • Congenital myopathy 4A, autosomal dominant (MIM#255310)
  • Congenital myopathy 4B, autosomal recessive (MIM#609284)
OMIM
191030
Clinvar variants
Variants in TPM3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: tpm3 has been classified as Green List (High Evidence).

1 Jun 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: tpm3 has been classified as Green List (High Evidence).

9 May 2023, Gel status: 0

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

Sangavi Sivagnanasundram (Melbourne Health)

gene: TPM3 was added gene: TPM3 was added to Muscular dystrophy_Paediatric. Sources: Other Mode of inheritance for gene: TPM3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TPM3 were set to 26418456; 18300303; 10619715; 12196661; 18382475 Phenotypes for gene: TPM3 were set to Congenital myopathy 4A, autosomal dominant (MIM#255310); Congenital myopathy 4B, autosomal recessive (MIM#609284) Review for gene: TPM3 was set to GREEN