KCNH2 Variant G47A

Summary of observed carriers, functional annotations, and structural context for KCNH2 G47A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

19%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

G47A has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 104% of WT with a standard error of 13%. 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 (%)
-3.149 0.951 1 0.774 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
Literature, cohort, and gnomAD – 0 0 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 G47A.
Neighbour residue Distance (Å) Observed variants
47 0 G47C, G47V,
50 4 E50X,
45 5 N45D, N45K, N45K,
46 5 D46Y, D46E, D46E,
48 5
28 5 K28E,
49 5 C49R, C49G,
51 6
27 7 R27X, R27P,
29 8 F29L, F29V, F29S, F29L, F29L,
52 8 C52W,
44 8 C44F, C44X, C44W,
26 8 S26I,
129 9 F129C,
53 9 G53S, G53R,
30 10 I30Del, I30T,
43 10 Y43D, Y43C,
56 10 R56Q,
23 11
128 11 N128S,
130 11 E130K,
55 11 S55L,
22 12 F22Y, F22S,
54 12 Y54N, Y54X,
100 12 R100G, R100Q, R100P,
59 12
25 12 Q25P,
131 12 V131L, V131L, V131fsX,
19 13 I19F,
127 13
24 13
106 13 F106L, F106V, F106L, F106L,
108 13 C108Y,
31 13 I31S
801 14 K801T,
69 14 L69Del, L69P,
98 14
802 14
101 14 K101E,
60 14 M60T,
800 14
126 14
58 15 E58K, E58D, E58D,
41 15 V41A,
109 15 L109X, L109Q, L109P,
803 15 D803Y, D803X,
110 15 V110A,
57 15 A57P,