KCNH2 Variant I560S

Summary of observed carriers, functional annotations, and structural context for KCNH2 I560S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

20%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I560S has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 44% of WT with a standard error of 19%. 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-5.741 0.969 -3 0.945 54

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 – 0 0 0 –
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 I560S.
Neighbour residue Distance (Å) Observed variants
560 0 I560fsX, I560M,
561 4 A561P, A561T, A561V,
559 5 L559F, L559H,
558 5 A558V, A558P, A558E,
563 6 W563X, W563G, W563C, W563C,
557 6
556 6
564 6 L564L,
562 7 H562R, H562Q, H562P, H562Q,
651 8 M651K,
622 8 L622F,
647 8
618 8 T618S, T618S,
619 9
555 9
648 9 G648A,
565 9
644 10 V644F, V644I,
655 10
422 10 A422T,
615 10 L615F, L615V,
554 10
566 11 C566F, C566S, C566G, C566R, C566S,
553 11 L553V,
567 11 I567T, I567M,
423 11
621 11 S621R, S621R, S621R, S621N
650 12 L650X,
623 12 T623I,
643 12
652 12 Y652X,
552 12 L552S,
646 12
656 12 F656L, F656L, F656L,
426 12 P426H,
640 12 F640L, F640V, F640L, F640L, F640Del,
419 12
532 12
654 13
649 13
529 13
620 13 S620G, S620I,
614 13 A614T, A614V,
617 13 F617L, F617V, F617L, F617L,
646 13
642 13 I642Del, I642V,
611 13 Y611D,
645 14 M645R, M645I, M645I, M645I, M645L, M645V, M645L,
653 14
649 14
568 14 W568C, W568C,
645 14 M645R, M645I, M645I, M645I, M645L, M645V, M645L,
551 14 F551L, F551L, F551L,
641 14 S641P, S641F,
421 14 T421fsX, T421M,
425 14
418 15
624 15 S624N, S624R, S624R, S624R,