KCNH2 Variant R56G

Summary of observed carriers, functional annotations, and structural context for KCNH2 R56G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

28%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R56G has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 5%. 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 (%)
-4.151 0.001 -4 0.673 76

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 – 0 0 0 –
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 R56G.
Neighbour residue Distance (Å) Observed variants
56 0 R56Q,
44 4 C44X, C44W, C44F,
55 6 S55L,
859 6 T859M, T859R,
60 6 M60T,
57 6 A57P,
803 7 D803X, D803Y,
59 7
43 7 Y43D, Y43C,
49 7 C49G, C49R,
46 8 D46E, D46E, D46Y,
45 8 N45K, N45D, N45K,
799 8 L799sp,
800 8
857 9 E857X,
58 9 E58D, E58D, E58K,
798 9 I798fsX,
48 9
802 9
804 9
860 10
41 10 V41A,
858 10 I858T, I858V,
42 10 I42N,
797 10 A797T,
47 10 G47V, G47C,
801 10 K801T,
54 11 Y54X, Y54N,
30 11 I30Del, I30T,
53 11 G53S, G53R,
61 11 Q61R,
782 11 I782N, I782fsX,
29 11 F29L, F29S, F29V, F29L, F29L,
52 11 C52W,
31 11 I31S,
50 12 E50X,
741 12 K741R,
805 12 F805C, F805S,
62 12 R62Q,
787 12
796 13 V796L, V796L, V796Del,
856 13
786 13
19 13 I19F,
789 13
740 13 C740W, C740G,
785 13 G785S, G785D, G785fsX,
40 13
861 13 N861H, N861I,
781 13
51 14
788 14 E788D, E788K, E788D,
28 14 K28E,
783 14 S783P,
806 14 G806R, G806R,
68 14 F68L, F68V, F68L, F68L,
32 14 A32T,
101 14 K101E,
855 15 S855R, S855R, S855R,
27 15 R27P, R27X,
63 15 P63H,
66 15 C66Y, C66G, C66R,