KCNH2 Variant E788K

Summary of observed carriers, functional annotations, and structural context for KCNH2 E788K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

25%

2/12 effective observations

Total carriers

2

1 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

E788K has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 76% of WT with a standard error of 17%. In our analysis we used SE < 20% as 'high quality'. Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.

Variant features alone are equivalent to phenotyping 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.732 1.0 1 0.968 68

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. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT2 Other Disease
19184172 2 1 1
Literature, cohort, and gnomAD – 2 1 1 –
Variant features alone – 10 9 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. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.

Previously observed variants near E788K.
Neighbour residue Distance (Å) Observed variants
788 0 E788K, E788D, E788D,
797 5 A797T,
787 5
798 5 I798fsX,
789 5
825 6
795 6 V795I,
790 6
824 6
823 7 R823W, R823fsX, R823T, R823Q,
786 7
12 7 N12D,
799 7 L799sp,
822 7 V822M, V822L, V822L,
796 8 V796L, V796L, V796Del,
15 8 L15V,
42 8 I42N,
13 9 T13N,
800 10
16 10 D16A,
10 10
794 10 V794I, V794D,
826 10 T826A, T826I,
821 10 D821E, D821E,
766 10
11 10 Q11L, Q11H, Q11H,
43 10 Y43D, Y43C,
785 10 G785S, G785fsX, G785D,
14 10
828 11
860 11
31 11 I31S,
820 11 G820R, G820R,
765 11
793 11 D793N,
767 11 D767X,
768 11
769 11
805 11 F805S, F805C,
19 12 I19F,
33 12 N33T
791 12 R791W, R791Q,
782 12 I782fsX, I782N,
803 12 D803Y, D803X,
763 12
770 12
124 12 M124T, M124R,
792 12
60 12 M60T,
32 13 A32T,
859 13 T859M, T859R,
41 13 V41A,
9 13 A9T, A9V,
764 13
17 13
18 13 I18M,
44 13 C44F, C44X, C44W,
40 13
819 14 N819K, N819K,
801 14 K801T,
56 14 R56Q,
771 14 H771fsX, H771R,
830 14
61 14 Q61R,
123 14
780 14
862 14 L862P,
827 14
804 15
36 15 V36X,
829 15 D829A, D829E, D829E,
806 15 G806R, G806R,