SCN1B

Chr 19ADAR

sodium voltage-gated channel beta subunit 1

Also known as: ATFB13, BRGDA5, DEE52, EIEE52, GEFSP1

NCBI Gene: 6324 ENSG00000105711 UniProt: Q07699

Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Atrial fibrillation, familial, 13MIM #615377

Brugada syndrome 5MIM #612838

Cardiac conduction defect, nonspecificMIM #612838

Developmental and epileptic encephalopathy 52MIM #617350

Generalized epilepsy with febrile seizures plus, type 1MIM #604233

517

ClinVar variants

Pathogenic / LP

0.10

pLI score

Active trials

Clinical Summary— SCN1B

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Gene-Disease Validity (ClinGen)

generalized epilepsy with febrile seizures plus · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 Pathogenic / Likely Pathogenic· 297 VUS of 517 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.26LOEUF

pLI 0.102

Z-score 1.22

OE 0.41 (0.17–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.22Z-score

OE missense 0.73 (0.63–0.85)

118 obs / 161.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.17–1.26)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.63–0.85)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01

0≤1.21.6

LoF obs/exp: 2 / 4.9Missense obs/exp: 118 / 161.8Syn Z: -0.06

ClinVar Variant Classifications

517 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic7

VUS297

Likely Benign145

Benign23

Conflicting18

Pathogenic

Likely Pathogenic

297

VUS

145

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	1	13	0	27
Likely Pathogenic	4	3	0	0	7
VUS	18	233	37	9	297
Likely Benign	0	6	46	93	145
Benign	0	1	21	1	23
Conflicting	—				18
Total	35	244	117	103	517

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.

Gene2Phenotype Curations

SCN1B-related Brugada syndrome

disputed

ADUndeterminedUncertain

Cardiac

G2P ↗

SCN1B-related developmental and epileptic encephalopathy

definitive

ARUndetermined Non-Loss-Of-FunctionAltered Gene Product Structure

Dev. Disorders

G2P ↗

splice region variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

SODIUM VOLTAGE-GATED CHANNEL, BETA SUBUNIT 1; SCN1B

MIM #600235 · *

Atrial fibrillation, familial, 13

MIM #615377