KCNH2 Variant G6R

Summary of observed carriers, functional annotations, and structural context for KCNH2 G6R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

1/18 effective observations

Total carriers

8

0 LQT2 · 3 unaffected

Functional studies

0

Publications with functional data

G6R is present in 8 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 11%. 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 (%)
-4.355 1.0 -3 0.825 33

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 – 8 3 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 G6R.
Neighbour residue Distance (Å) Observed variants
6 0 G6R,
481 4
5 5
7 5
482 6 V482A,
699 6 E699D, E699D,
8 6
4 7
476 7 V476I,
480 8 E480V,
695 8
403 9
402 9 H402R,
765 9
9 9 A9T, A9V,
702 9
698 9 E698X, E698K,
483 10 V483I,
477 10
478 10 A478D,
3 10
703 10
475 10 Y475Del, Y475C,
474 11 T474I,
764 11
766 11
827 11
479 11
696 11 R696H, R696C,
10 11
401 12
484 12
700 12
767 13 D767X,
697 13 L697X,
694 13 R694C, R694H,
692 13
701 13
706 13 S706F, S706C
404 14
826 14 T826A, T826I,
691 14
704 14 A704V, A704T,
763 14
693 14 L693X,
825 14
824 14
473 15 T473P,
541 15 R541C, R541H,
13 15 T13N,
540 15 D540fsX,