KCNH2 Variant V482A

Summary of observed carriers, functional annotations, and structural context for KCNH2 V482A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

19%

2/12 effective observations

Total carriers

2

1 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

V482A 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 10%. 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 (%)
-3.707 0.993 0 0.948 46

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 2 1 1
Literature, cohort, and gnomAD – 2 1 1 –
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 V482A.
Neighbour residue Distance (Å) Observed variants
482 0 V482A,
481 4
483 4 V483I,
480 5 E480V,
6 6 G6R,
8 6
476 6 V476I,
484 7
475 7 Y475Del, Y475C,
9 7 A9T, A9V,
477 8
474 8 T474I,
7 8
402 9 H402R,
5 9
478 9 A478D,
488 10 R488H, R488C,
479 10
403 10
401 10
4 10
10 11
485 11 H485X,
765 11
489 11 I489I, I489F,
699 12 E699D, E699D,
473 12 T473P,
827 12
13 12 T13N,
492 13 H492Y,
695 13
400 13 I400N,
3 13
399 13
766 13
826 13 T826A, T826I,
764 14
487 14 G487S, G487R,
486 14
825 14
404 14
11 14 Q11H, Q11L, Q11H,
702 14
703 14
698 15 E698X, E698K,