Congenital myopathy 22A, classic: genes and variants
Congenital myopathy 22A, classic is linked to 1 analyzed protein (SCN4A). 8 DNA variants are known to cause it; 85 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Congenital myopathy 22A, classic
SCN4A: Sodium channel protein type 4 subunit alpha
Its rapid sodium current initiates and propagates skeletal-muscle action potentials. Gain- and loss-of-function variants cause disorders of muscle excitability including sodium-channel myotonia, paramyotonia congenita, periodic paralysis, and some congenital myopathies.
8 disease-causing and 85 uncertain variants in SCN4A are linked to Congenital myopathy 22A, classic.
Where Congenital myopathy 22A, classic variants cluster
- SCN4A S4 of repeat II (positions 665–682): 3 of 8 disease-causing changes, 38.2× more than its size predicts.
Known disease-causing variants in Congenital myopathy 22A, classic
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SCN4A R669H | 669 | II | Disease-causing (★★) |
| SCN4A R672H | 672 | II | Disease-causing (★★) |
| SCN4A R675Q | 675 | II | Disease-causing (★★) |
| SCN4A R1135C | 1135 | III | Disease-causing (★★) |
| SCN4A I1455T | 1455 | IV | Disease-causing (★★) |
| SCN4A M1592V | 1592 | IV | Disease-causing (★★) |
| SCN4A E1702K | 1702 | Cytoplasmic | Disease-causing (★★) |
| SCN4A C375R | 375 | I | Disease-causing |
Same protein, different disease
- Hyperkalemic periodic paralysis is also caused by SCN4A variants; they fall mostly in different places as the Congenital myopathy 22A, classic variants (62 disease-causing).
- Paramyotonia congenita of Von Eulenburg is also caused by SCN4A variants; they fall mostly in different places as the Congenital myopathy 22A, classic variants (15 disease-causing).
- Potassium-aggravated myotonia is also caused by SCN4A variants; they fall mostly in different places as the Congenital myopathy 22A, classic variants (14 disease-causing).
- Hypokalemic periodic paralysis is also caused by SCN4A variants; they fall partly in the same places as the Congenital myopathy 22A, classic variants (11 disease-causing).
- Congenital myasthenic syndrome 17 is also caused by SCN4A variants; they fall mostly in different places as the Congenital myopathy 22A, classic variants (7 disease-causing).
Diseases related to Congenital myopathy 22A, classic
- Amyotrophic lateral sclerosis, also linked to SCN4A
- Cardiac arrhythmia, also linked to SCN4A
- Sotos syndrome, also linked to SCN4A
- Hyperkalemic periodic paralysis, also linked to SCN4A
- Hypokalemic periodic paralysis, also linked to SCN4A
- Congenital myasthenic syndrome 17, also linked to SCN4A
- Skeletal muscle channelopathy, also linked to SCN4A
- Epilepsy, also linked to SCN4A
- Paramyotonia congenita of Von Eulenburg, also linked to SCN4A
- Potassium-aggravated myotonia, also linked to SCN4A
- Fetal akinesia deformation sequence, also linked to SCN4A
- Focal epilepsy, also linked to SCN4A
Frequently asked questions
Which genes are linked to Congenital myopathy 22A, classic?
In CATVariant, Congenital myopathy 22A, classic is linked to 1 analyzed protein: SCN4A (Sodium channel protein type 4 subunit alpha).
How many genetic variants are linked to Congenital myopathy 22A, classic?
93 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 85 are of uncertain significance or have conflicting reports.
Which uncertain variants in Congenital myopathy 22A, classic look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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