KCNH2 Variant C52G

Summary of observed carriers, functional annotations, and structural context for KCNH2 C52G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

23%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

C52G 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 8%. 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 (%)
-2.539 0.51 -4 0.672 57

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 C52G.
Neighbour residue Distance (Å) Observed variants
52 0 C52W,
53 4 G53S, G53R,
51 4
54 5 Y54N, Y54X,
49 5 C49R, C49G,
48 5
100 6 R100G, R100Q, R100P,
101 7 K101E,
69 7 L69Del, L69P,
50 7 E50X,
55 8 S55L,
47 8 G47C, G47V,
68 8 F68L, F68V, F68L, F68L,
106 9 F106L, F106V, F106L, F106L,
102 9 D102H, D102V, D102X,
59 9
98 9
104 10
58 10 E58K, E58D, E58D,
28 10 K28E,
99 10 Y99N, Y99S,
103 10
129 10 F129C,
44 10 C44F, C44X, C44W,
45 10 N45D, N45K, N45K,
66 11 C66R, C66G, C66Y,
46 11 D46Y, D46E, D46E,
105 11
56 11 R56Q,
30 12 I30Del, I30T
108 12 C108Y,
70 12 H70R, H70Q, H70Q,
57 12 A57P,
97 12
29 13 F29L, F29V, F29S, F29L, F29L,
62 13 R62Q,
60 13 M60T,
131 13 V131L, V131L, V131fsX,
67 13
127 14
130 14 E130K,
41 14 V41A,
107 14 L107P,
71 14 G71R, G71R, G71W, G71E,
96 14 I96V, I96T,
27 14 R27X, R27P,
43 14 Y43D, Y43C,
128 14 N128S,
65 14 T65P,
110 14 V110A,
64 15 C64R, C64Y,
63 15 P63H,
857 15 E857X,