SCN5A Variant K1236R

Summary of observed carriers, functional annotations, and structural context for SCN5A K1236R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/12 effective observations

Estimated BrS1 penetrance

40%

4/12 effective observations

Total carriers

2

1 BrS1 · 0 LQT3 · 1 unaffected

K1236R 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 3 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 (%)
-2.15 0.571 2.92 0.755 60 1

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
21126620 2010 1 0 1 0
Literature, cohort, and gnomAD 2 1 0 1
Variant features alone 15 12 0 3

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)
21126620 2010

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 K1236R.
Neighbour residue Distance (Å) Observed variants
1233 5 K1233E,
1243 12 D1243N,
1234 7
1285 15
1299 13 c.3894delC,
1298 14 P1298L,
1241 12
1226 11
1221 13 A1221V,
1242 11
1239 7 L1239P,
1244 14 K1244E,
1235 6
1231 10 E1231K,
1237 5 V1237F,
1289 14
1228 12 Y1228H, Y1228F, Y1228C,
1223 14 c.3667delG,
1222 13 p.L1222LfsX7, L1222R,
1230 6 E1230K,
1227 12
1229 5
1301 14
1224 13
1240 7 E1240Q,
1225 8 E1225K, G1225K,
1232 11 R1232Q, R1232W,
1238 8
1236 0 K1236N, K1236R, K1236N,
1303 12 R1303Q, R1303W,