Rhabdomyolysis and Metabolic Myopathy

Gene: TWNK

Green List (high evidence)

TWNK (twinkle mtDNA helicase)
EnsemblGeneIds (GRCh38): ENSG00000107815
EnsemblGeneIds (GRCh37): ENSG00000107815
OMIM: 606075, Gene2Phenotype
TWNK is in 19 panels

3 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

PMID: 32234020: Fig 1 shows variant distribution for all condition: - Missense within the linker region have only been reported for PEOA (AD). No other patterns for AD vs AR missense. - Missense in N-terminal motifs generally cause PEOA - PTCs reported for AR conditions - Same variant has been reported for both AR Perrault and mito depletion conditions (p.N399S). PMID: 18593709: Missense transfected into Schneider cells could form hexamers, had no effect on protein expression, had both loss and gain of mtDNA copy numbers and loss of ATPase activity when overexpressed with endogenous protein. No evidence of GOF mechanism found.
Created: 29 Jul 2020, 12:08 a.m. | Last Modified: 29 Jul 2020, 12:08 a.m.
Panel Version: 0.449

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286

Publications

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

PMID: 32234020: Fig 1 shows variant distribution for all condition:
- Missense within the linker region have only been reported for PEOA (AD). No other patterns for AD vs AR missense.
- Missense in N-terminal motifs generally cause PEOA
- PTCs reported for AR conditions
- Same variant has been reported for both AR Perrault and mito depletion conditions (p.N399S).

PMID: 18593709: Missense transfected into Schneider cells could form hexamers, had no effect on protein expression, had both loss and gain of mtDNA copy numbers and loss of ATPase activity when overexpressed with endogenous protein
No evidence of GOF mechanism found
Created: 28 Jul 2020, 11:51 p.m. | Last Modified: 28 Jul 2020, 11:51 p.m.
Panel Version: 0.3551

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286

Publications

Mode of pathogenicity
Other

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

Exercise intolerance reported as a presenting feature of the condition in at least 5 cases.
Sources: Expert list
Created: 29 May 2020, 12:48 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert Review Green
  • Expert list
  • Victorian Clinical Genetics Services
  • Australian Genomics Health Alliance Mitochondrial Flagship
Phenotypes
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286
OMIM
606075
Clinvar variants
Variants in TWNK
Penetrance
None
Publications
Panels with this gene

History Filter Activity

7 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

29 May 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

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

29 May 2020, Gel status: 1

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

Bryony Thompson (Royal Melbourne Hospital)

gene: TWNK was added gene: TWNK was added to Rhabdomyolysis RMH. Sources: Expert list Mode of inheritance for gene: TWNK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TWNK were set to 20880070 Phenotypes for gene: TWNK were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MIM#609286 Review for gene: TWNK was set to GREEN