KCNH2 Variant D803Y

Summary of observed carriers, functional annotations, and structural context for KCNH2 D803Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

28%

90% CI: 10.1% – 51.0%

3/12 effective observations

Total carriers

2

1 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

D803Y 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 (%)
-8.285 1.0 -3 0.976 56

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
30244407 2018 2 1 1
Literature, cohort, and gnomAD – 2 1 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 D803Y.
Neighbour residue Distance (Å) Observed variants
803 0 D803Y, D803X,
800 5
782 5 I782fsX, I782N,
802 5
804 5
799 5 L799sp,
859 6 T859M, T859R,
56 7 R56Q,
801 7 K801T,
781 7
805 7 F805S, F805C,
783 8 S783P,
787 8
858 9 I858V, I858T,
785 9 G785S, G785fsX, G785D,
798 9 I798fsX,
44 10 C44F, C44X, C44W,
860 10
786 10
740 10 C740G, C740W,
857 10 E857X,
830 10
780 10
43 10 Y43D, Y43C,
736 10
57 11 A57P,
46 11 D46Y, D46E, D46E,
797 11 A797T,
831 11
60 11 M60T,
741 11 K741R,
806 11 G806R, G806R,
55 11 S55L,
856 11
779 11
828 11
784 12 R784G, R784W, R784Q,
735 12 S735L,
829 12 D829A, D829E, D829E,
789 12
45 12 N45D, N45K, N45K,
739 12 H739fsX,
788 12 E788K, E788D, E788D,
49 13 C49R, C49G,
42 13 I42N,
742 13
822 13 V822M, V822L, V822L,
59 13
861 13 N861H, N861I,
824 14
743 14
862 14 L862P,
826 14 T826A, T826I,
19 14 I19F
825 14
796 14 V796L, V796L, V796Del,
832 14
58 14 E58K, E58D, E58D,
855 14 S855R, S855R, S855R,
761 14
61 14 Q61R,
778 14 A778T,
769 14
763 14
737 15 L737P,
833 15
41 15 V41A,
16 15 D16A,
47 15 G47C, G47V,