Fetal anomalies
Gene: SCN4A

SCN4A (sodium voltage-gated channel alpha subunit 4)
EnsemblGeneIds (GRCh38): ENSG00000007314
EnsemblGeneIds (GRCh37): ENSG00000007314
OMIM: 603967, Gene2Phenotype
SCN4A is in 14 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

According to Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust), the relevant phenotypes associated with SCN4A variants for the Fetal anomalies panel are Classic congenital myopathy-22A (OMIM:620351) and Severe fetal congenital myopathy-22B (OMIM:620369), both of which are recessive. Therefore, the mode of inheritance should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal.
Created: 7 Apr 2025, 11:59 a.m. | Last Modified: 7 Apr 2025, 11:59 a.m.

Panel Version: 5.88

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 7 Apr 2025, 11:59 a.m.
Last Modified: 7 Apr 2025, 11:59 a.m.
Panel version: 5.88

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

Change to mode of inheritance - currently listed as MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown, however SCN4A is associated with both dominant and recessive disorders and only the recessive phenotypes (congenital myopathy-22A/B, OMIM 620351/620369) are relevant to the fetal anomalies panel.
Created: 10 Oct 2024, 7:22 a.m. | Last Modified: 10 Oct 2024, 7:22 a.m.

Panel Version: 4.198

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Classic congenital myopathy-22A, 620351; Severe fetal congenital myopathy-22B, 620369

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

Created: 10 Oct 2024, 7:22 a.m.
Last Modified: 10 Oct 2024, 7:22 a.m.
Panel version: 4.198

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Green on arthrogryposis panel, and phenotypes include polyhydramnios, arthrogryposis (variable penetrance). Therefore promote from Red to Green.
Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.

Panel Version: 0.311

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted SCN4A gene rating from Green to Red.
Created: 30 Apr 2019, 8:24 a.m.

DDG2P rating in original PAGE list: Confirmed for HYPOKALEMIC PERIODIC PARALYSIS, Confirmed for HYPERKALEMIC PERIODIC PARALYSIS TYPE 1 and Confirmed for PARAMYOTONIA CONGENITA OF VON EULENBURG.
Created: 11 Dec 2018, 9:05 a.m.

In the original PAGE file, MOP listed as Activating for HYPERKALEMIC PERIODIC PARALYSIS TYPE 1, and listed as All missense/in frame for HYPOKALEMIC PERIODIC PARALYSIS and PARAMYOTONIA CONGENITA OF VON EULENBURG.
Created: 8 Nov 2018, 4:45 p.m.

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.311

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Classic congenital myopathy-22A, OMIM:620351
congenital myopathy 22A, classic,MONDO:0957247:Severe fetal congenital myopathy-22B, OMIM:620369
congenital myopathy 22B, severe fetal, MONDO:0957265

Tags

Q2_25_ MOI

OMIM

603967

Clinvar variants

Variants in SCN4A

Penetrance

None

Panels with this gene

History Filter Activity

30 Oct 2025, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_expert_review was removed from gene: SCN4A.

7 Apr 2025, Gel status: 3

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_25_ MOI tag was added to gene: SCN4A. Tag Q2_25_expert_review tag was added to gene: SCN4A.

7 Apr 2025, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SCN4A were changed from PARAMYOTONIA CONGENITA OF VON EULENBURG; HYPERKALEMIC PERIODIC PARALYSIS TYPE 1; HYPOKALEMIC PERIODIC PARALYSIS to Classic congenital myopathy-22A, OMIM:620351; congenital myopathy 22A, classic,MONDO:0957247:Severe fetal congenital myopathy-22B, OMIM:620369; congenital myopathy 22B, severe fetal, MONDO:0957265

25 Jul 2019, Gel status: 3