Skeletal muscle channelopathy

Gene: SCN4A

Green List (high evidence)

SCN4A (sodium voltage-gated channel alpha subunit 4)
EnsemblGeneIds (GRCh38): ENSG00000007314
EnsemblGeneIds (GRCh37): ENSG00000007314
OMIM: 603967, Gene2Phenotype
SCN4A is in 16 panels

3 reviews

Eleanor Williams (Genomics England Curator)

PMID: 26700687 - Zaharieva et al 2016 - Through whole exome sequencing, they identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected individuals showed in utero- or neonatal-onset muscle weakness. In 7 cases, death occurred during the third trimester or shortly after birth due to severe muscle weakness. In the other 4 cases there was congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities.
Created: 17 Mar 2021, 1:55 p.m. | Last Modified: 17 Mar 2021, 1:55 p.m.
Panel Version: 1.21

Louise Daugherty (Genomics England Curator)

I don't know

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:57 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dominant: Hyperkalemic periodic paralysis (170500); Hypokalemic periodic paralysis, type 2 (613345); Paramyotonia congenita (168300). Recessive: Congenital myopathy.

Publications

  • Miller et al 2004 Neurology 9, 1647-55 PMID: 15534250. Matthews et al 2009 Neurology 72, 1544-7 PMID:19118277. Matthews et al 2008 Neurology 70, 50-3 PMID: 18166706. Zaharieva et al 2016 Brain 139, 674-91 PMID: 26700687

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • London North GLH
Phenotypes
  • Hypokalemic periodic paralysis, type 2 OMIM:613345
  • Hyperkalemic periodic paralysis, type 2 OMIM:170500
  • Paramyotonia congenita OMIM:168300
  • Congenital myopathy MONDO:0019952.
OMIM
603967
Clinvar variants
Variants in SCN4A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Mar 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SCN4A were changed from Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis, type 2 OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy MONDO:0019952. to Hypokalemic periodic paralysis, type 2 OMIM:613345; Hyperkalemic periodic paralysis, type 2 OMIM:170500; Paramyotonia congenita OMIM:168300; Congenital myopathy MONDO:0019952.

16 Mar 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SCN4A were changed from Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis, type 2 OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy. to Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis, type 2 OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy MONDO:0019952.

16 Mar 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SCN4A were changed from Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy. to Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis, type 2 OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy.

16 Mar 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SCN4A were changed from Hypokalemic periodic paralysis, type 2 (613345); Dominant: Hyperkalemic periodic paralysis (170500); Paramyotonia congenita (168300). Recessive: Congenital myopathy. to Hypokalemic periodic paralysis, type 2 OMIM:613345; Dominant: Hyperkalemic periodic paralysis OMIM:170500; Paramyotonia congenita OMIM:168300. Recessive: Congenital myopathy.

25 Oct 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene SCN4A were changed from to 18166706; 15534250; 19118277; 26700687

25 Oct 2019, Gel status: 3

Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene SCN4A was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes Hypokalemic periodic paralysis, type 2 (613345); Dominant: Hyperkalemic periodic paralysis (170500); Paramyotonia congenita (168300). Recessive: Congenital myopathy. for gene: SCN4A

28 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to SCN4A. Rating Changed from Red List (low evidence) to Green List (high evidence)

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SCN4A.

28 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: SCN4A was added gene: SCN4A was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: SCN4A was set to