KCNH2 Variant E480G

Summary of observed carriers, functional annotations, and structural context for KCNH2 E480G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

28%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

E480G has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 105% of WT with a standard error of 25%. 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 (%)
-4.444 0.041 -2 0.722 71

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 – 0 0 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 E480G.
Neighbour residue Distance (Å) Observed variants
480 0 E480V,
481 4
477 4
479 5
478 5 A478D,
482 5 V482A,
483 7 V483I,
476 7 V476I,
475 8 Y475C, Y475Del,
6 8 G6R,
827 8
9 9 A9T, A9V,
8 10
765 10
488 10 R488C, R488H,
7 10
484 10
826 10 T826A, T826I,
4 10
474 11 T474I,
492 11 H492Y,
10 12
13 12 T13N,
764 12
703 12
489 12 I489F, I489I,
5 12
825 12
402 12 H402R,
699 12 E699D, E699D,
16 13 D16A,
766 13
20 14 R20G, R20L
485 14 H485X,
17 14
491 14 V491I,
702 14
828 14
706 14 S706C, S706F,
824 14
487 14 G487S, G487R,
763 14
403 15
473 15 T473P,
786 15