SCN5A Variant K1233E

Summary of observed carriers, functional annotations, and structural context for SCN5A K1233E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

17%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

K1233E is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_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 (%)
-3.08 0.021 -0.32 0.627 23 2

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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

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

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 K1233E.
Neighbour residue Distance (Å) Observed variants
1231 8 E1231K,
1241 15
1226 14
1233 0 K1233E,
1237 7 V1237F,
1228 12 Y1228H, Y1228C, Y1228F,
1230 5 E1230K,
1227 13
1240 11 E1240Q
1225 12 E1225K, G1225K,
1234 6
1229 7
1239 11 L1239P,
1232 8 R1232W, R1232Q,
1238 10
1236 5 K1236R, K1236N, K1236N,
1235 8