KCNH2 Variant D793N

Summary of observed carriers, functional annotations, and structural context for KCNH2 D793N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

6%

90% CI: 0.3% – 22.0%

0/14 effective observations

Total carriers

4

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

D793N is present in 4 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 110% of WT with a standard error of 11%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.755 0.9 1 0.636 7

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 – 4 2 0 –
Variant features alone – 10 10 0 –

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 D793N.
Neighbour residue Distance (Å) Observed variants
793 0 D793N,
792 3
794 5 V794I, V794D,
790 7
795 8 V795I,
791 9 R791W, R791Q,
821 9 D821E, D821E,
11 9 Q11L, Q11H, Q11H,
823 9 R823W, R823fsX, R823T, R823Q,
12 10 N12D,
35 10 R35W,
796 11 V796L, V796L, V796Del,
789 11
820 11 G820R, G820R,
788 11 E788K, E788D, E788D,
33 11 N33T
36 12 V36X,
822 12 V822M, V822L, V822L,
123 12
797 13 A797T,
772 13
10 13
34 13 A34T,
771 13 H771fsX, H771R,
819 13 N819K, N819K,
768 14
748 14
124 14 M124T, M124R,
766 14
42 14 I42N,
14 14
824 14
15 15 L15V,
37 15
13 15 T13N,
825 15
770 15