SCN5A Variant E1231K

Summary of observed carriers, functional annotations, and structural context for SCN5A E1231K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

1/14 effective observations

Estimated BrS1 penetrance

12%

1/14 effective observations

Total carriers

4

0 BrS1 · 1 LQT3 · 3 unaffected

E1231K is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-1.06 0.037 0.8 0.549 19 12

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
15840476 2005 1 1 0 0
Literature, cohort, and gnomAD – 4 3 1 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
15840476 2005

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near E1231K.
Neighbour residue Distance (Å) Observed variants
1231 0 E1231K,
1226 11
1233 8 K1233E,
1695 12 Q1695X
1237 13 V1237F,
1228 6 Y1228H, Y1228C, Y1228F,
1223 15 c.3667delG,
1681 13 c.5040_5042delTTAinsC, Y1681F,
1224 12
1697 14
1230 6 E1230K,
1227 8
1225 12 E1225K, G1225K,
1234 10
1229 7
1239 14 L1239P,
1232 6 R1232W, R1232Q,
331 15
1238 14
1236 10 K1236R, K1236N, K1236N,
1235 9
1696 12