KCNH2 Variant G806R

Summary of observed carriers, functional annotations, and structural context for KCNH2 G806R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

26%

90% CI: 21.8% – 65.5%

5/13 effective observations

Total carriers

3

3 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

G806R has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 7% of WT with a standard error of 3%. 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 (%)
-7.434 1.0 -3 0.451 80

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
Italy Cohort 2020 2 0 2
France Cohort 2020 1 0 1
Literature, cohort, and gnomAD – 3 0 3 –
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 G806R.
Neighbour residue Distance (Å) Observed variants
806 0 G806R, G806R,
807 4 E807X,
862 5 L862P,
805 5 F805S, F805C,
861 6 N861H, N861I,
779 6
858 6 I858V, I858T,
776 6 L776I, L776P,
808 7
860 7
778 7 A778T,
780 7
804 7
859 8 T859M, T859R,
818 9 S818A, S818W, S818L,
816 9 G816V,
809 9
777 10
819 10 N819K, N819K,
781 10
770 10
820 10 G820R, G820R,
835 10 R835W, R835fsX, R835Q,
789 11
822 11 V822M, V822L, V822L,
833 11
812 11 Y812S,
863 11 R863X, R863P
856 11
803 11 D803Y, D803X,
799 11 L799sp,
775 11
774 12 D774Y, D774X,
832 12
817 12
857 12 E857X,
769 12
853 12 W853X,
815 12
57 12 A57P,
782 12 I782fsX, I782N,
811 12
834 12 H834R,
810 13
787 13
773 13
797 13 A797T,
821 13 D821E, D821E,
61 13 Q61R,
838 13 L838R,
772 13
60 13 M60T,
830 13
771 14 H771fsX, H771R,
852 14
831 14
796 14 V796L, V796L, V796Del,
56 14 R56Q,
813 14
791 14 R791W, R791Q,
800 14
790 14
839 15
758 15
788 15 E788K, E788D, E788D,