KCNH2 Variant S783P

Summary of observed carriers, functional annotations, and structural context for KCNH2 S783P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

16%

90% CI: 10.3% – 49.6%

3/13 effective observations

Total carriers

3

2 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

S783P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 2% of WT with a standard error of 2%. 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 (%)
-4.622 0.997 -1 0.936 46

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 3 1 2
Literature, cohort, and gnomAD – 3 1 2 –
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 S783P.
Neighbour residue Distance (Å) Observed variants
783 0 S783P,
784 4 R784G, R784W, R784Q,
782 5 I782fsX, I782N,
829 5 D829A, D829E, D829E,
801 5 K801T,
802 6
785 6 G785S, G785fsX, G785D,
735 7 S735L,
830 7
831 7
800 7
828 8
736 8
803 8 D803Y, D803X,
781 8
786 10
739 10 H739fsX,
762 10
787 10
733 10
740 10 C740G, C740W,
799 10 L799sp,
734 10 R734C, R734H,
761 10
804 11
760 11
763 11
826 11 T826A, T826I,
780 12
805 12 F805S, F805C,
732 12
737 12 L737P,
738 12 Q738X,
827 12
758 13
832 13
824 13
825 14
779 14
731 14 H731R,
764 14
759 14 K759N, K759N,
56 14 R56Q,
743 14
859 14 T859M, T859R,
798 14 I798fsX,
46 14 D46Y, D46E, D46E,
707 14
741 15 K741R,
833 15
687 15
769 15
16 15 D16A