KCNH2 Variant R823T

Summary of observed carriers, functional annotations, and structural context for KCNH2 R823T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

30%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R823T has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 76% of WT with a standard error of 7%. 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 (%)
None None None None 72

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
27871843 2017 1 0 1
Literature, cohort, and gnomAD – 1 0 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 R823T.
Neighbour residue Distance (Å) Observed variants
823 0 R823W, R823fsX, R823T, R823Q,
822 5 V822M, V822L, V822L,
768 6
790 6
824 6
821 6 D821E, D821E,
766 6
788 7 E788K, E788D, E788D,
767 7 D767X,
789 8
769 8
825 8
787 8
771 9 H771fsX, H771R,
770 9
12 9 N12D,
10 9
820 9 G820R, G820R,
793 9 D793N,
765 9
11 10 Q11L, Q11H, Q11H,
795 10 V795I,
797 10 A797T,
792 10
764 11
794 11 V794I, V794D,
763 11
786 11
796 11 V796L, V796L, V796Del,
772 11
723 11 C723R, C723G, C723X,
826 11 T826A, T826I,
791 12 R791W, R791Q,
696 12 R696C, R696H,
13 12 T13N,
828 12
798 12 I798fsX,
799 12 L799sp,
7 12
9 12 A9T, A9V,
805 13 F805S, F805C,
819 13 N819K, N819K,
8 13
15 13 L15V,
724 13 L724X,
774 14 D774Y, D774X,
748 14
818 14 S818A, S818W, S818L,
752 14 R752W, R752Q, R752P,
780 14
860 14
42 14 I42N,
785 14 G785S, G785fsX, G785D,
14 14
830 14
827 14
727 14
16 14 D16A
800 14
862 14 L862P,
773 15
699 15 E699D, E699D,
782 15 I782fsX, I782N,