KCNH2 Variant Q11H

Summary of observed carriers, functional annotations, and structural context for KCNH2 Q11H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

11%

1/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

Q11H has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 120% of WT with a standard error of 22%. 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 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.717 0.897 -1 0.882 3

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
France Cohort 2020 1 1 0
Literature, cohort, and gnomAD – 1 1 0 –
Variant features alone – 10 9 1 –

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 Q11H.
Neighbour residue Distance (Å) Observed variants
11 0 Q11L, Q11H, Q11H,
12 4 N12D,
10 5
13 7 T13N,
9 7 A9T, A9V,
14 8
8 9
793 9 D793N,
823 10 R823W, R823fsX, R823T, R823Q,
825 10
15 10 L15V,
795 10 V795I,
788 10 E788K, E788D, E788D,
766 10
7 11
790 11
824 11
794 11 V794I, V794D,
123 12
765 12
117 12
792 12
16 13 D16A,
124 13 M124T, M124R,
17 13
826 13 T826A, T826I,
767 14 D767X,
118 14 E118K, E118X, E118D, E118D,
786 14
789 14
33 14 N33T
797 14 A797T,
821 14 D821E, D821E,
798 14 I798fsX,
482 14 V482A,
822 14 V822M, V822L, V822L,
768 14
796 14 V796L, V796L, V796Del,
787 14
115 14 V115M,
18 14 I18M,
119 15 D119H, D119G,
121 15 A121fsX,
35 15 R35W,
481 15