KCNH2 Variant A9T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A9T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

10%

1/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

A9T is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 88% of WT with a standard error of 20%. 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 (%)
-2.175 0.886 -1 0.576 4

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 – 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 A9T.
Neighbour residue Distance (Å) Observed variants
9 0 A9T, A9V,
10 3
8 4
13 6 T13N,
7 6
11 7 Q11L, Q11H, Q11H,
482 7 V482A,
765 8
481 8
825 8
12 9 N12D,
766 9
480 9 E480V,
6 9 G6R,
826 10 T826A, T826I,
14 10
483 10 V483I,
824 10
16 11 D16A
484 11
827 12
764 12
17 12
823 12 R823W, R823fsX, R823T, R823Q,
15 12 L15V,
767 12 D767X,
479 12
699 13 E699D, E699D,
5 13
788 13 E788K, E788D, E788D,
477 13
786 13
695 13
476 13 V476I,
488 13 R488C, R488H,
478 14 A478D,
485 14 H485X,
696 14 R696C, R696H,
828 14
763 14
475 14 Y475C, Y475Del,
474 14 T474I,
403 15
787 15