KCNH2 Variant P632S

Summary of observed carriers, functional annotations, and structural context for KCNH2 P632S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

46%

90% CI: 28.4% – 72.5%

6/13 effective observations

Total carriers

3

3 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

P632S 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 (%)
-7.734 0.998 -1 0.948 93

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
22727609 2012 1 0 1
Japan Cohort 2020 1 0 1
10973849 2000 1 0 1
Literature, cohort, and gnomAD – 3 0 3 –
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 P632S.
Neighbour residue Distance (Å) Observed variants
632 0 P632A, P632S,
631 4 S631F,
633 5 N633D, N633S, N633I,
638 5 K638E, K638D, K638Del, K638R,
637 5 E637K, E637G, E637X,
629 6 N629D, N629T, N629S, N629I, N629K, N629K,
616 6 Y616S,
634 6 T634P, T634A, T634S, T634S, T634I,
627 7 F627L, F627fsX, F627X, F627L, F627L,
641 7 S641P, S641F,
630 7 V630I, V630T, V630A,
617 8 F617L, F617V, F617L, F617L,
585 8 W585C, W585C,
568 8 W568C, W568C,
584 8 G584S, G584R, G584C,
628 8 G628S, G628R, G628Del, G628D, G628A, G628V,
636 8
640 9 F640L, F640V, F640Del, F640L, F640L,
635 9 N635I,
630 9 V630I, V630T, V630A,
613 9 T613A, T613L, T613K, T613M,
628 9 G628S, G628R, G628Del, G628D, G628A, G628V,
639 9 I639F, I639N,
592 10 Q592X,
642 10 I642V, I642Del,
588 10 N588D, N588K, N588K,
612 10 V612L, V612L, V612A,
621 10 S621R, S621N, S621R, S621R,
626 10 G626S, G626A, G626V,
571 11 I571L, I571V,
620 11 S620G, S620I,
645 11 M645L, M645V, M645L, M645R, M645I, M645I, M645I
626 11 G626S, G626A, G626V,
593 11 I593V, I593K, I593T, I593R, I593X,
583 11 I583V,
629 11 N629D, N629T, N629S, N629I, N629K, N629K,
644 11 V644I, V644F,
625 11 V625E,
589 11 L589P,
617 12 F617L, F617V, F617L, F617L,
620 12 S620G, S620I,
618 12 T618S, T618S,
586 12 L586M,
609 12 D609N, D609G,
572 12 G572S, G572R, G572C, G572D,
614 12 A614T, A614V,
614 12 A614T, A614V,
615 12 L615V, L615F,
643 12
631 13 S631F,
613 13 T613A, T613L, T613K, T613M,
627 13 F627L, F627fsX, F627X, F627L, F627L,
616 13 Y616S,
589 13 L589P,
619 13
587 13
588 13 N588D, N588K, N588K,
575 13 E575K,
564 14 L564L,
565 14
625 14 V625E,
618 14 T618S, T618S,
567 14 I567T, I567M,
627 14 F627L, F627fsX, F627X, F627L, F627L,
570 14
592 14 Q592X,
585 14 W585C, W585C,
621 14 S621R, S621N, S621R, S621R,
590 15 G590D, G590V,
622 15 L622F,
628 15 G628S, G628R, G628Del, G628D, G628A, G628V,
608 15
569 15 Y569H, Y569C, Y569X,
623 15 T623I,
611 15 Y611D,
624 15 S624R, S624N, S624R, S624R,
626 15 G626S, G626A, G626V,
591 15 D591N, D591H,