KCNH2 Variant A430V

Summary of observed carriers, functional annotations, and structural context for KCNH2 A430V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

16%

1/11 effective observations

Total carriers

1

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A430V is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 50% of WT with a standard error of 23%. 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 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.673 0.243 0 0.9 60

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 – 1 0 0 –
Variant features alone – 10 9 1 –

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 A430V.
Neighbour residue Distance (Å) Observed variants
430 0
429 4 A429P, A429V,
431 4 F431L, F431L, F431L,
432 6
428 6 S428fsX, S428X, S428L,
566 6 C566S, C566R, C566G, C566S, C566F,
569 6 Y569H, Y569C, Y569X,
426 6 P426H,
427 7 Y427H, Y427S, Y427C,
570 7
573 9
567 9 I567T, I567M,
425 9
522 9 G522E,
565 9
523 9
574 10 M574L, M574V, M574L,
611 10 Y611D,
610 10
607 10
562 11 H562P, H562R, H562Q, H562Q,
526 11
572 11 G572S, G572R, G572C, G572D,
571 11 I571L, I571V,
525 11 K525N, K525N,
424 11
563 11 W563G, W563C, W563C, W563X,
423 12
568 12 W568C, W568C,
614 12 A614T, A614V,
520 12
564 12 L564L,
422 13 A422T,
524 13
521 13
529 14
586 14 L586M,
615 14 L615V, L615F
528 14 R528W, R528X, R528P,
609 14 D609N, D609G,
585 14 W585C, W585C,
561 14 A561T, A561P, A561V,
612 14 V612L, V612L, V612A,
606 14 S606Del, S606P, S606F,
421 14 T421fsX, T421M,
613 14 T613A, T613L, T613K, T613M,
608 14
575 15 E575K,
527 15
452 15
576 15
605 15 P605L,