KCNH2 Variant I571V

Summary of observed carriers, functional annotations, and structural context for KCNH2 I571V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

34%

90% CI: 17.6% – 64.1%

4/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I571V has not been reported in gnomAD. This residue resides in a 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 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-0.948 0.999 3 0.766 89

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
24103226 2014 1 0 1 Seizures
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 I571V.
Neighbour residue Distance (Å) Observed variants
571 0 I571L, I571V,
570 4
572 4 G572S, G572R, G572C, G572D,
568 6 W568C, W568C,
636 6
637 6 E637K, E637G, E637X,
575 6 E575K,
567 7 I567T, I567M,
574 7 M574L, M574V, M574L,
573 7
569 7 Y569H, Y569C, Y569X,
640 8 F640L, F640V, F640Del, F640L, F640L,
585 8 W585C, W585C,
634 8 T634P, T634A, T634S, T634S, T634I,
586 10 L586M,
566 10 C566S, C566R, C566G, C566S, C566F,
565 10
639 10 I639F, I639N,
584 10 G584S, G584R, G584C,
576 10
564 11 L564L,
635 11 N635I,
632 11 P632A, P632S,
430 11
614 11 A614T, A614V,
638 11 K638E, K638D, K638Del, K638R,
641 11 S641P, S641F,
617 11 F617L, F617V, F617L, F617L,
633 12 N633D, N633S, N633I,
431 12 F431L, F431L, F431L,
610 12
583 12 I583V,
643 12
577 12
631 12 S631F,
618 13 T618S, T618S,
587 13
644 13 V644I, V644F
613 13 T613A, T613L, T613K, T613M,
630 13 V630I, V630T, V630A,
642 14 I642V, I642Del,
429 14 A429P, A429V,
588 14 N588D, N588K, N588K,
589 14 L589P,
611 14 Y611D,
615 14 L615V, L615F,
426 15 P426H,
561 15 A561T, A561P, A561V,
563 15 W563G, W563C, W563C, W563X,
562 15 H562P, H562R, H562Q, H562Q,
616 15 Y616S,
621 15 S621R, S621N, S621R, S621R,
612 15 V612L, V612L, V612A,