SCN5A Variant K126E

Summary of observed carriers, functional annotations, and structural context for SCN5A K126E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

50%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

K126E has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
-3.7 0.919 -1.06 0.926 74 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
12051963 2002 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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)
23805106 2013 HEK 89 2.8 3.4
12051963 2002
20129283 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 K126E.
Neighbour residue Distance (Å) Observed variants
126 0 K126E,
175 13 K175N, K175N,
129 7
178 10 A178G,
128 8 c.381dupT,
117 14
119 10 P119S, P119L,
179 12 R179X, R179Q
177 12 L177P,
123 4 A123G, A123V,
121 9 R121W, R121Q,
127 6
124 6 A124D,
118 13
125 5 V125L, V125L,
131 12
174 11 V174I,
133 11
115 14 S115G,
173 15
132 13 c.393-5C>A,
114 15
130 8
170 14 F170I,
116 12
134 13 N134S,
120 10
122 7