KCNH2 Variant I642Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 I642Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

39%

4/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I642Del has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
None None None None 79

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
19038855 2009 1 0 1 Seizure
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 7 3 –

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 I642Del.
Neighbour residue Distance (Å) Observed variants
642 0 I642V, I642Del,
641 4 S641P, S641F,
645 5 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
643 5
639 5 I639F, I639N,
619 6
616 6 Y616S,
644 6 V644I, V644F,
615 7 L615V, L615F,
646 7
640 7 F640L, F640V, F640Del, F640L, F640L,
638 7 K638E, K638D, K638Del, K638R,
612 8 V612L, V612L, V612A,
620 8 S620G, S620I,
618 9 T618S, T618S,
647 9
621 10 S621R, S621N, S621R, S621R,
623 10 T623I,
632 10 P632A, P632S,
558 10 A558P, A558E, A558V,
614 10 A614T, A614V,
561 10 A561T, A561P, A561V,
613 10 T613A, T613L, T613K, T613M,
636 10
627 10 F627L, F627fsX, F627X, F627L, F627L,
637 10 E637K, E637G, E637X,
648 10 G648A,
557 11
611 11 Y611D,
617 11 F617L, F617V, F617L, F617L,
649 11
625 11 V625E,
635 11 N635I,
622 11 L622F,
621 12 S621R, S621N, S621R, S621R,
622 12 L622F,
562 12 H562P, H562R, H562Q, H562Q,
617 12 F617L, F617V, F617L, F617L,
565 12
634 12 T634P, T634A, T634S, T634S, T634I,
626 12 G626S, G626A, G626V,
568 12 W568C, W568C,
564 12 L564L,
618 12 T618S, T618S,
554 12
624 13 S624R, S624N, S624R, S624R,
609 13 D609N, D609G,
631 13 S631F,
630 13 V630I, V630T, V630A,
629 13 N629D, N629T, N629S, N629I, N629K, N629K,
650 13 L650X,
624 13 S624R, S624N, S624R, S624R,
620 13 S620G, S620I,
633 13 N633D, N633S, N633I,
560 13 I560fsX, I560M,
608 13
559 13 L559F, L559H,
564 14 L564L,
571 14 I571L, I571V,
567 14 I567T, I567M,
626 14 G626S, G626A, G626V,
555 14
628 14 G628S, G628R, G628Del, G628D, G628A, G628V,
652 14 Y652X
623 15 T623I,
651 15 M651K,
556 15
566 15 C566S, C566R, C566G, C566S, C566F,
568 15 W568C, W568C,