Paramyotonia congenita of Von Eulenburg: genes and variants
Paramyotonia congenita of Von Eulenburg is linked to 1 analyzed protein (SCN4A). 15 DNA variants are known to cause it; 158 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 Paramyotonia congenita of Von Eulenburg
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.
15 disease-causing and 158 uncertain variants in SCN4A are linked to Paramyotonia congenita of Von Eulenburg.
Where Paramyotonia congenita of Von Eulenburg variants cluster
- SCN4A Cytoplasmic (positions 1292–1354): 3 of 15 disease-causing changes, 5.8× more than its size predicts.
- SCN4A II (positions 560–832): 5 of 15 disease-causing changes, 2.2× more than its size predicts.
- SCN4A IV (positions 1335–1633): 5 of 15 disease-causing changes, 2.0× more than its size predicts.
Known disease-causing variants in Paramyotonia congenita of Von Eulenburg
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SCN4A R675W | 675 | II | Disease-causing (★★) |
| SCN4A T704M | 704 | II | Disease-causing (★★) |
| SCN4A V1293I | 1293 | III | Disease-causing (★★) |
| SCN4A V1589M | 1589 | IV | Disease-causing (★★) |
| SCN4A L689F | 689 | II | Disease-causing (★★) |
| SCN4A I693T | 693 | II | Disease-causing (★★) |
| SCN4A I1455T | 1455 | IV | Disease-causing (★★) |
| SCN4A M1592I | 1592 | IV | Disease-causing (★★) |
| SCN4A F1705I | 1705 | Cytoplasmic | Disease-causing (★★) |
| SCN4A G1306E | 1306 | III | Disease-causing (★★) |
| SCN4A N1297K | 1297 | III | Disease-causing (★) |
| SCN4A F1473S | 1473 | IV | Disease-causing (★) |
| SCN4A L703P | 703 | II | Disease-causing |
| SCN4A L1433R | 1433 | IV | Disease-causing |
| SCN4A I141V | 141 | I | Disease-causing |
Which prediction tools work for Paramyotonia congenita of Von Eulenburg
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 92 out of 100
Same protein, different disease
- Hyperkalemic periodic paralysis is also caused by SCN4A variants; they fall mostly in different places as the Paramyotonia congenita of Von Eulenburg variants (62 disease-causing).
- Potassium-aggravated myotonia is also caused by SCN4A variants; they fall partly in the same places as the Paramyotonia congenita of Von Eulenburg variants (14 disease-causing).
- Hypokalemic periodic paralysis is also caused by SCN4A variants; they fall partly in the same places as the Paramyotonia congenita of Von Eulenburg variants (11 disease-causing).
- Congenital myopathy 22A, classic is also caused by SCN4A variants; they fall partly in the same places as the Paramyotonia congenita of Von Eulenburg variants (8 disease-causing).
- Congenital myasthenic syndrome 17 is also caused by SCN4A variants; they fall mostly in different places as the Paramyotonia congenita of Von Eulenburg variants (7 disease-causing).
Diseases related to Paramyotonia congenita of Von Eulenburg
- 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
- Potassium-aggravated myotonia, 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 Paramyotonia congenita of Von Eulenburg?
In CATVariant, Paramyotonia congenita of Von Eulenburg is linked to 1 analyzed protein: SCN4A (Sodium channel protein type 4 subunit alpha).
How many genetic variants are linked to Paramyotonia congenita of Von Eulenburg?
182 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 158 are of uncertain significance or have conflicting reports.
Which uncertain variants in Paramyotonia congenita of Von Eulenburg look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Paramyotonia congenita of Von Eulenburg?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.92, based on 13 disease-causing and 19 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.
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