KCNH2 Variant I567T

Summary of observed carriers, functional annotations, and structural context for KCNH2 I567T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

23%

2/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

I567T has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 0%. 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 (%)
-4.849 0.999 -1 0.915 35

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
Italy Cohort 2020 1 1 0
Literature, cohort, and gnomAD – 1 1 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 I567T.
Neighbour residue Distance (Å) Observed variants
567 0 I567T, I567M,
566 5 C566S, C566R, C566G, C566S, C566F,
564 5 L564L,
565 6
570 6
568 7 W568C, W568C,
571 7 I571L, I571V,
640 7 F640L, F640V, F640Del, F640L, F640L,
569 8 Y569H, Y569C, Y569X,
563 8 W563G, W563C, W563C, W563X,
430 9
562 9 H562P, H562R, H562Q, H562Q,
561 9 A561T, A561P, A561V,
426 9 P426H,
614 9 A614T, A614V,
618 9 T618S, T618S,
572 10 G572S, G572R, G572C, G572D,
644 10 V644I, V644F,
643 10
431 10 F431L, F431L, F431L,
574 10 M574L, M574V, M574L,
573 11
617 11 F617L, F617V, F617L, F617L,
429 11 A429P, A429V,
560 11 I560fsX, I560M,
637 11 E637K, E637G, E637X,
636 11
615 11 L615V, L615F,
611 11 Y611D,
585 11 W585C, W585C,
641 11 S641P, S641F,
639 12 I639F, I639N,
427 12 Y427H, Y427S, Y427C,
559 12 L559F, L559H,
575 13 E575K,
647 13
425 13
526 13
613 13 T613A, T613L, T613K, T613M,
610 13
621 13 S621R, S621N, S621R, S621R,
428 13 S428fsX, S428X, S428L,
422 13 A422T,
523 13
622 13 L622F,
423 13
529 14
619 14
558 14 A558P, A558E, A558V,
642 14 I642V, I642Del,
586 14 L586M,
632 14 P632A, P632S,
634 14 T634P, T634A, T634S, T634S, T634I,
612 14 V612L, V612L, V612A,
638 14 K638E, K638D, K638Del, K638R,
432 14
645 15 M645L, M645V, M645L, M645R, M645I, M645I, M645I
620 15 S620G, S620I,
630 15 V630I, V630T, V630A,