KCNH2 Variant L564L

Summary of observed carriers, functional annotations, and structural context for KCNH2 L564L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

%

NA/NA effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L564L has not been reported in gnomAD. This residue resides in a None region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of %. 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.

In silico predictors

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

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
Japan Cohort 2020 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 NA NA –

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 L564L.
Neighbour residue Distance (Å) Observed variants
564 0 L564L,
565 5
561 5 A561T, A561P, A561V,
567 5 I567T, I567M,
618 5 T618S, T618S,
560 6 I560fsX, I560M,
563 6 W563G, W563C, W563C, W563X,
566 6 C566S, C566R, C566G, C566S, C566F,
640 7 F640L, F640V, F640Del, F640L, F640L,
644 7 V644I, V644F,
562 7 H562P, H562R, H562Q, H562Q,
568 8 W568C, W568C,
615 8 L615V, L615F,
614 8 A614T, A614V,
617 8 F617L, F617V, F617L, F617L,
622 9 L622F,
643 9
619 9
647 9
559 9 L559F, L559H,
621 9 S621R, S621N, S621R, S621R,
558 10 A558P, A558E, A558V,
641 10 S641P, S641F,
570 10
571 11 I571L, I571V,
557 11
648 11 G648A,
426 11 P426H,
611 11 Y611D,
620 11 S620G, S620I,
569 11 Y569H, Y569C, Y569X,
645 12 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
651 12 M651K
556 12
613 12 T613A, T613L, T613K, T613M,
430 12
637 12 E637K, E637G, E637X,
642 12 I642V, I642Del,
423 12
422 12 A422T,
616 13 Y616S,
623 13 T623I,
646 13
639 13 I639F, I639N,
431 13 F431L, F431L, F431L,
585 13 W585C, W585C,
612 13 V612L, V612L, V612A,
636 13
427 13 Y427H, Y427S, Y427C,
642 14 I642V, I642Del,
572 14 G572S, G572R, G572C, G572D,
630 14 V630I, V630T, V630A,
632 14 P632A, P632S,
649 14
529 14
429 14 A429P, A429V,
425 14
650 14 L650X,
645 14 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
555 15
610 15
624 15 S624R, S624N, S624R, S624R,
638 15 K638E, K638D, K638Del, K638R,
631 15 S631F,
627 15 F627L, F627fsX, F627X, F627L, F627L,
573 15