KCNH2 Variant K638E

Summary of observed carriers, functional annotations, and structural context for KCNH2 K638E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

48%

6/14 effective observations

Total carriers

4

4 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

K638E has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.862 1.0 1 0.879 88

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
11854117 2002 3 0 3
10973849 2000 1 0 1
22378279 1 0
Literature, cohort, and gnomAD – 4 0 4 –
Variant features alone – 10 8 2 –

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 K638E.
Neighbour residue Distance (Å) Observed variants
638 0 K638E, K638D, K638Del, K638R,
616 5 Y616S,
632 5 P632A, P632S,
635 5 N635I,
637 5 E637K, E637G, E637X,
634 6 T634P, T634A, T634S, T634S, T634I,
612 6 V612L, V612L, V612A,
639 6 I639F, I639N,
613 6 T613A, T613L, T613K, T613M,
641 6 S641P, S641F,
636 6
633 6 N633D, N633S, N633I,
642 7 I642V, I642Del,
609 8 D609N, D609G,
629 8 N629D, N629T, N629S, N629I, N629K, N629K,
640 8 F640L, F640V, F640Del, F640L, F640L,
615 8 L615V, L615F,
631 8 S631F,
614 9 A614T, A614V,
627 9 F627L, F627fsX, F627X, F627L, F627L,
630 9 V630I, V630T, V630A,
611 10 Y611D,
608 10
645 10 M645L, M645V, M645L, M645R, M645I, M645I, M645I
617 10 F617L, F617V, F617L, F617L,
568 11 W568C, W568C,
593 11 I593V, I593K, I593T, I593R, I593X,
620 11 S620G, S620I,
589 11 L589P,
592 11 Q592X,
643 11
619 11
584 11 G584S, G584R, G584C,
571 11 I571L, I571V,
628 11 G628S, G628R, G628Del, G628D, G628A, G628V,
644 11 V644I, V644F,
617 12 F617L, F617V, F617L, F617L,
610 12
585 12 W585C, W585C,
618 12 T618S, T618S,
630 12 V630I, V630T, V630A,
621 12 S621R, S621N, S621R, S621R,
606 12 S606Del, S606P, S606F,
626 12 G626S, G626A, G626V,
583 13 I583V,
575 13 E575K,
585 13 W585C, W585C,
625 13 V625E,
565 13
572 13 G572S, G572R, G572C, G572D,
631 13 S631F,
628 14 G628S, G628R, G628Del, G628D, G628A, G628V,
607 14
646 14
568 14 W568C, W568C,
588 14 N588D, N588K, N588K,
605 14 P605L,
621 14 S621R, S621N, S621R, S621R,
590 14 G590D, G590V,
626 14 G626S, G626A, G626V,
561 14 A561T, A561P, A561V,
588 14 N588D, N588K, N588K,
618 14 T618S, T618S,
586 14 L586M,
623 14 T623I,
567 14 I567T, I567M,
595 15 K595E, K595N, K595N,
620 15 S620G, S620I,
594 15
564 15 L564L,
570 15
562 15 H562P, H562R, H562Q, H562Q,