Epilepsy with myoclonic atonic seizures: genes and variants

Genes linked to Epilepsy with myoclonic atonic seizures

• SLC6A1: Sodium- and chloride-dependent GABA transporter 1

  It clears GABA from extracellular space into neurons and glial cells, regulating the duration and spatial spread of inhibitory neurotransmission. Haploinsufficiency or dysfunctional variants cause SLC6A1-related neurodevelopmental disorder, commonly with myoclonic-atonic epilepsy, developmental delay, and autism-related features.

  55 disease-causing and 213 uncertain variants in SLC6A1 are linked to Epilepsy with myoclonic atonic seizures.

Where Epilepsy with myoclonic atonic seizures variants cluster

• SLC6A1 Extracellular (positions 74–80): 5 of 55 disease-causing changes, 7.8× more than its size predicts.
• SLC6A1 Transmembrane (positions 321–342): 5 of 55 disease-causing changes, 2.5× more than its size predicts.
• SLC6A1 Transmembrane (positions 292–309): 4 of 55 disease-causing changes, 2.4× more than its size predicts.
• SLC6A1 Transmembrane (positions 498–517): 4 of 55 disease-causing changes, 2.2× more than its size predicts.
• SLC6A1 Extracellular (positions 343–374): 5 of 55 disease-causing changes, 1.7× more than its size predicts.

Known disease-causing variants in Epilepsy with myoclonic atonic seizures

Uncertain variants in Epilepsy with myoclonic atonic seizures that look disease-causing

Which prediction tools work for Epilepsy with myoclonic atonic seizures

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

• REVEL: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 93 out of 100
• AlphaMissense: 92 out of 100
• MetaLR: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 89 out of 100
• PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 72 out of 100

Diseases related to Epilepsy with myoclonic atonic seizures

• Epilepsy, also linked to SLC6A1

Frequently asked questions

Which genes are linked to Epilepsy with myoclonic atonic seizures?

In CATVariant, Epilepsy with myoclonic atonic seizures is linked to 1 analyzed protein: SLC6A1 (Sodium- and chloride-dependent GABA transporter 1).

How many genetic variants are linked to Epilepsy with myoclonic atonic seizures?

351 variants: 55 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 213 are of uncertain significance or have conflicting reports.

Which uncertain variants in Epilepsy with myoclonic atonic seizures look disease-causing?

6 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example SLC6A1 A334S, SLC6A1 S456C, SLC6A1 A305T, SLC6A1 R44P and SLC6A1 G297V. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Epilepsy with myoclonic atonic seizures?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 13 disease-causing and 44 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