Severe myoclonic epilepsy in infancy: genes and variants

Genes linked to Severe myoclonic epilepsy in infancy

• SCN1A: Sodium channel protein type 1 subunit alpha

  Its sodium current is especially important for reliable firing of inhibitory interneurons and therefore for balancing excitation across neural networks. Loss-of-function variants are the major cause of Dravet syndrome, while other variants cause GEFS+ or familial hemiplegic migraine.

  213 disease-causing and 62 uncertain variants in SCN1A are linked to Severe myoclonic epilepsy in infancy.

• HCN1: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

  The protein forms a hyperpolarization-activated channel that conducts both potassium and sodium ions. It contributes to pacemaker currents and the neuronal I(h) current that shapes excitability, and HCN1 variants are associated with developmental epilepsy syndromes.

  1 disease-causing and 0 uncertain variants in HCN1 are linked to Severe myoclonic epilepsy in infancy.

Weakly linked (only a few uncertain records): SCN9A.

Where Severe myoclonic epilepsy in infancy variants cluster

• SCN1A I (positions 110–454): 67 of 213 disease-causing changes, 1.8× more than its size predicts.
• SCN1A S5 of repeat III (positions 1346–1369): 9 of 213 disease-causing changes, 3.5× more than its size predicts.
• SCN1A Cytoplasmic (positions 1656–1665): 5 of 213 disease-causing changes, 4.7× more than its size predicts.
• SCN1A S4 of repeat IV (positions 1637–1655): 6 of 213 disease-causing changes, 3.0× more than its size predicts.
• SCN1A S6 of repeat IV (positions 1760–1788): 7 of 213 disease-causing changes, 2.3× more than its size predicts.

Known disease-causing variants in Severe myoclonic epilepsy in infancy

Showing 60 of 214.

Which prediction tools work for Severe myoclonic epilepsy in infancy

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100
• CADD: 90 out of 100
• EVE: 90 out of 100
• AlphaMissense: 88 out of 100
• MutPred2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 72 out of 100

Same protein, different disease

• Early-infantile DEE is also caused by SCN1A variants; they fall in the same places as the Severe myoclonic epilepsy in infancy variants (422 disease-causing).
• Generalized epilepsy with febrile seizures plus is also caused by SCN1A variants; they fall in the same places as the Severe myoclonic epilepsy in infancy variants (76 disease-causing).
• Migraine, familial hemiplegic, 1 is also caused by SCN1A variants; they fall in the same places as the Severe myoclonic epilepsy in infancy variants (20 disease-causing).
• Autosomal dominant epilepsy is also caused by SCN1A variants; they fall in the same places as the Severe myoclonic epilepsy in infancy variants (4 disease-causing).
• Epilepsy is also caused by SCN1A variants; they fall in the same places as the Severe myoclonic epilepsy in infancy variants (4 disease-causing).
• Early-infantile DEE is also caused by HCN1 variants; they fall mostly in different places as the Severe myoclonic epilepsy in infancy variants (14 disease-causing).
• Generalized epilepsy with febrile seizures plus is also caused by HCN1 variants; they fall mostly in different places as the Severe myoclonic epilepsy in infancy variants (10 disease-causing).

Diseases related to Severe myoclonic epilepsy in infancy

• Early-infantile DEE, also linked to HCN1 and SCN1A
• Generalized epilepsy with febrile seizures plus, also linked to HCN1 and SCN1A
• Genetic developmental and epileptic encephalopathy, also linked to HCN1 and SCN1A
• Amyotrophic lateral sclerosis, also linked to SCN1A
• Cardiac arrhythmia, also linked to SCN1A
• Migraine, familial hemiplegic, 1, also linked to SCN1A
• Febrile seizures, familial, 3a, also linked to SCN1A
• Epilepsy, also linked to SCN1A
• Autosomal dominant epilepsy, also linked to SCN1A
• Focal epilepsy, also linked to SCN1A
• Lennox-Gastaut syndrome, also linked to SCN1A
• Undetermined early-onset epileptic encephalopathy, also linked to HCN1

Frequently asked questions

Which genes are linked to Severe myoclonic epilepsy in infancy?

In CATVariant, Severe myoclonic epilepsy in infancy is linked to 2 analyzed proteins: SCN1A (Sodium channel protein type 1 subunit alpha) and HCN1 (Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1).

How many genetic variants are linked to Severe myoclonic epilepsy in infancy?

336 variants: 214 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 65 are of uncertain significance or have conflicting reports.

Which uncertain variants in Severe myoclonic epilepsy in infancy 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 Severe myoclonic epilepsy in infancy?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 206 disease-causing and 147 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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