KCNH2 Variant N479K

Summary of observed carriers, functional annotations, and structural context for KCNH2 N479K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

25%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

N479K has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 130% of WT with a standard error of 31%. 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 (%)
-5.56 0.991 0 0.684 38

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 N479K.
Neighbour residue Distance (Å) Observed variants
479 0
478 4 A478D,
480 5 E480V,
477 5
827 6
481 7
826 9 T826A, T826I,
476 9 V476I,
482 10 V482A,
765 10
703 11
483 11 V483I,
475 11 Y475Del, Y475C,
6 11 G6R,
764 11
828 12
4 12
20 12 R20G, R20L,
706 12 S706C, S706F,
9 12 A9T, A9V,
825 12
784 12 R784Q, R784G, R784W,
785 13 G785fsX, G785S, G785D,
492 13 H492Y,
829 13 D829E, D829E, D829A,
488 13 R488C, R488H,
16 13 D16A,
763 13
7 13
707 13
762 13
8 13
13 13 T13N,
786 14
699 14 E699D, E699D,
10 14
824 14
702 14
17 14
484 14
766 14
704 15 A704T, A704V,