KCNH2 Variant I782N

Summary of observed carriers, functional annotations, and structural context for KCNH2 I782N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

30%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I782N 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-6.427 1.0 -4 0.954 75

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
26496715 2015 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 I782N.
Neighbour residue Distance (Å) Observed variants
782 0 I782fsX, I782N,
783 5 S783P,
803 5 D803Y, D803X,
800 5
830 6
781 6
802 6
801 7 K801T,
799 7 L799sp,
785 7 G785S, G785fsX, G785D,
804 7
831 7
787 7
805 7 F805S, F805C,
829 7 D829A, D829E, D829E,
828 8
780 8
784 8 R784G, R784W, R784Q,
786 8
736 9
735 9 S735L,
859 10 T859M, T859R,
761 10
763 10
779 11
740 11 C740G, C740W,
832 11
762 11
56 11 R56Q,
798 11 I798fsX,
824 11
826 11 T826A, T826I,
760 12
858 12 I858V, I858T,
769 12
822 12 V822M, V822L, V822L,
806 12 G806R, G806R,
739 12 H739fsX,
788 12 E788K, E788D, E788D,
733 12
860 12
825 12
758 12
797 12 A797T,
789 12
833 13
778 13 A778T,
43 13 Y43D, Y43C,
737 13 L737P,
759 14 K759N, K759N,
764 14
44 14 C44F, C44X, C44W,
857 14 E857X,
856 14
827 14
743 14
741 14 K741R,
46 14 D46Y, D46E, D46E,
770 14
734 14 R734C, R734H,
16 14 D16A
767 14 D767X,
742 14
732 15
60 15 M60T,
738 15 Q738X,
57 15 A57P,
765 15
823 15 R823W, R823fsX, R823T, R823Q,