SCN1B
Chr 19ADARsodium voltage-gated channel beta subunit 1
Also known as: ATFB13, BRGDA5, DEE52, EIEE52, GEFSP1
The protein encodes the beta-1 subunit of voltage-gated sodium channels, which modulates the kinetics of channel inactivation during action potential generation and propagation in muscle and neuronal cells. Mutations cause generalized epilepsy with febrile seizures plus, developmental and epileptic encephalopathy, Brugada syndrome, and cardiac conduction defects through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function effects on sodium channel activity.
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
124 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 1 | 5 | 0 | 9 |
Likely Pathogenic | 0 | 2 | 0 | 0 | 2 |
VUS | 4 | 36 | 3 | 1 | 44 |
Likely Benign | 0 | 4 | 12 | 24 | 40 |
Benign | 0 | 3 | 9 | 1 | 13 |
Conflicting | — | 16 | |||
| Total | 7 | 46 | 29 | 26 | 124 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCN1B · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools