SCN5A Variant E48K

Summary of observed carriers, functional annotations, and structural context for SCN5A E48K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

2/29 effective observations

Estimated BrS1 penetrance

3%

0/29 effective observations

Total carriers

19

0 BrS1 · 2 LQT3 · 17 unaffected

E48K is present in 17 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-1.95 0.997 0.63 0.723 0 8

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
26746457 2016 1 1 0 0
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 19 17 2 0 –
Variant features alone – 15 15 0 0 – –

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)
25904541 2015 HEK 63 4 -3
26746457 2016
19716085 2009

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 E48K.
Neighbour residue Distance (Å) Observed variants
33 15
34 14 R34C, R34H,
35 14 G35S,
36 13
37 13 T37A,
38 12
39 11 L39F, L39F,
40 11
41 10
42 9
43 8 R43X, R43Q,
44 8
45 7 G45A,
46 5
47 4
48 0 E48K,
49 4 E49K,
50 5
51 7 A51V,
52 8 P52S, P52H
53 8 R53Q,
54 9
55 10 Q55X,
56 11
57 11
58 12
59 13
60 13 A60P,
61 14
62 14 K62T,
63 15 K63N, K63N,