KCNH2 Variant E698K

Summary of observed carriers, functional annotations, and structural context for KCNH2 E698K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

0/13 effective observations

Total carriers

3

0 LQT2 · 3 unaffected

Functional studies

0

Publications with functional data

E698K is present in 3 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 104% of WT with a standard error of 10%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.872 0.941 1 0.906 3

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
Literature, cohort, and gnomAD – 3 3 0 –
Variant features alone – 10 10 0 –

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 E698K.
Neighbour residue Distance (Å) Observed variants
698 0 E698K, E698X,
697 5 L697X,
694 5 R694C, R694H,
699 6 E699D, E699D,
695 6
702 7
5 7
701 7
680 8
677 8 M677T,
681 8 R681W,
696 9 R696C, R696H,
693 9 L693X,
684 9
4 9
3 9
700 9
6 9 G6R,
691 10
689 10
692 11
7 11
690 11
703 11
720 11
673 11
544 11 E544A, E544fsX,
683 11
403 12
704 12 A704T, A704V,
724 12 L724X,
678 12
676 12 Q676fsX, Q676X,
685 13 R685C, R685H, R685P,
705 13 W705fsX, W705X,
728 13
674 13 H674Y, H674fsX,
481 13
682 13 E682X,
706 13 S706C, S706F,
540 13 D540fsX,
716 13 V716G,
402 13 H402R,
764 14
727 14
541 14 R541C, R541H,
476 14 V476I,
679 14 R679W, R679Q,
719 14
8 14
767 14 D767X
765 14
766 14
721 14 P721L,
687 15
543 15 S543fsX,
675 15
545 15
717 15 L717P,
688 15
482 15 V482A,