Potassium-aggravated myotonia: genes and variants
Potassium-aggravated myotonia is linked to 1 analyzed protein (SCN4A). 14 DNA variants are known to cause it; 124 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Potassium-aggravated myotonia
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.
14 disease-causing and 124 uncertain variants in SCN4A are linked to Potassium-aggravated myotonia.
Where Potassium-aggravated myotonia variants cluster
- SCN4A S4 of repeat II (positions 665–682): 4 of 14 disease-causing changes, 29.1× more than its size predicts.
- SCN4A IV (positions 1335–1633): 4 of 14 disease-causing changes, 1.8× more than its size predicts.
Known disease-causing variants in Potassium-aggravated myotonia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SCN4A R222W | 222 | I | Disease-causing (★★) |
| SCN4A R669H | 669 | II | Disease-causing (★★) |
| SCN4A R672H | 672 | II | Disease-causing (★★) |
| SCN4A R1135H | 1135 | III | Disease-causing (★★) |
| SCN4A R1448H | 1448 | IV | Disease-causing (★★) |
| SCN4A R1460Q | 1460 | IV | Disease-causing (★★) |
| SCN4A R675Q | 675 | II | Disease-causing (★★) |
| SCN4A M1592I | 1592 | IV | Disease-causing (★★) |
| SCN4A M1592V | 1592 | IV | Disease-causing (★★) |
| SCN4A V445M | 445 | I | Disease-causing (★★) |
| SCN4A G1306V | 1306 | III | Disease-causing (★★) |
| SCN4A E1702K | 1702 | Cytoplasmic | Disease-causing (★★) |
| SCN4A S670Y | 670 | II | Disease-causing (★) |
| SCN4A S1159P | 1159 | III | Disease-causing (★) |
Uncertain variants in Potassium-aggravated myotonia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| SCN4A R1135P | 1135 | III | Uncertain (★) | +6: in a 3D region that tolerates change poorly (1R); R1135H at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
Which prediction tools work for Potassium-aggravated myotonia
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 95 out of 100
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 92 out of 100
- phyloP: 85 out of 100
Same protein, different disease
- Hyperkalemic periodic paralysis is also caused by SCN4A variants; they fall partly in the same places as the Potassium-aggravated myotonia variants (62 disease-causing).
- Paramyotonia congenita of Von Eulenburg is also caused by SCN4A variants; they fall mostly in different places as the Potassium-aggravated myotonia variants (15 disease-causing).
- Hypokalemic periodic paralysis is also caused by SCN4A variants; they fall in the same places as the Potassium-aggravated myotonia variants (11 disease-causing).
- Congenital myopathy 22A, classic is also caused by SCN4A variants; they fall mostly in different places as the Potassium-aggravated myotonia variants (8 disease-causing).
- Congenital myasthenic syndrome 17 is also caused by SCN4A variants; they fall mostly in different places as the Potassium-aggravated myotonia variants (7 disease-causing).
Diseases related to Potassium-aggravated myotonia
- 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
- Congenital myopathy 22A, classic, 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 Potassium-aggravated myotonia?
In CATVariant, Potassium-aggravated myotonia is linked to 1 analyzed protein: SCN4A (Sodium channel protein type 4 subunit alpha).
How many genetic variants are linked to Potassium-aggravated myotonia?
148 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 124 are of uncertain significance or have conflicting reports.
Which uncertain variants in Potassium-aggravated myotonia look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example SCN4A R1135P. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Potassium-aggravated myotonia?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.95, based on 9 disease-causing and 18 harmless variants).
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.
Download every variant as CSV · Browse all diseases · Methods · About the Center