KCNH2 Variant A797T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A797T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

36%

4/12 effective observations

Total carriers

2

2 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A797T has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 93% 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.857 0.996 0 0.95 73

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 2 0 2
Literature, cohort, and gnomAD – 2 0 2 –
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 A797T.
Neighbour residue Distance (Å) Observed variants
797 0 A797T,
796 4 V796L, V796L, V796Del,
789 4
798 4 I798fsX,
42 5 I42N,
788 5 E788K, E788D, E788D,
795 6 V795I,
799 6 L799sp,
860 7
790 7
787 7
60 8 M60T,
43 8 Y43D, Y43C,
41 8 V41A,
61 9 Q61R,
794 9 V794I, V794D,
822 9 V822M, V822L, V822L,
31 9 I31S,
859 9 T859M, T859R,
40 9
786 9
800 10
33 10 N33T
791 10 R791W, R791Q,
15 10 L15V,
44 10 C44F, C44X, C44W,
32 10 A32T,
823 10 R823W, R823fsX, R823T, R823Q,
56 10 R56Q,
820 10 G820R, G820R,
805 10 F805S, F805C,
12 10 N12D,
821 11 D821E, D821E,
803 11 D803Y, D803X,
825 11
824 11
819 11 N819K, N819K,
862 11 L862P,
124 12 M124T, M124R,
59 12
57 12 A57P,
36 12 V36X,
30 12 I30Del, I30T,
792 12
19 12 I19F,
782 12 I782fsX, I782N,
16 12 D16A,
804 13
861 13 N861H, N861I,
785 13 G785S, G785fsX, G785D,
793 13 D793N,
806 13 G806R, G806R,
14 13
39 13 C39R, C39X,
770 13
858 13 I858V, I858T,
13 13 T13N,
34 14 A34T,
62 14 R62Q,
35 14 R35W,
769 14
45 14 N45D, N45K, N45K,
828 14
826 14 T826A, T826I,
29 14 F29L, F29V, F29S, F29L, F29L,
801 14 K801T,
11 14 Q11L, Q11H, Q11H,
123 14
780 14
18 14 I18M,
818 14 S818A, S818W, S818L,
10 14
768 14
125 14
63 14 P63H,
64 15 C64R, C64Y,
766 15
55 15 S55L,
126 15
802 15