KCNH2 Variant C39G

Summary of observed carriers, functional annotations, and structural context for KCNH2 C39G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

16%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

C39G has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 89% of WT with a standard error of 16%. 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 (%)
-7.298 0.995 -4 0.867 37

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 C39G.
Neighbour residue Distance (Å) Observed variants
39 0 C39R, C39X,
40 4
38 5
64 5 C64R, C64Y,
36 5 V36X,
32 6 A32T,
34 6 A34T,
33 6 N33T
63 6 P63H,
125 7
41 7 V41A,
37 7
35 8 R35W,
86 8 L86R,
65 8 T65P,
124 9 M124T, M124R,
42 10 I42N,
31 10 I31S,
62 10 R62Q,
796 10 V796L, V796L, V796Del,
87 10 L87P,
66 10 C66R, C66G, C66Y,
83 10 A83P, A83fsX,
61 11 Q61R,
123 11
122 11
30 11 I30Del, I30T,
795 11 V795I,
127 11
794 11 V794I, V794D,
85 12 A85P, A85V,
60 12 M60T,
82 12 I82Del, I82dup, I82Ins, I82T,
126 12
67 12
59 13
114 13 P114S,
112 13 V112M,
797 13 A797T,
791 14 R791W, R791Q,
88 14
115 14 V115M,
89 14 A89G, A89V,
68 14 F68L, F68V, F68L, F68L,
84 14
113 14 V113Del,
43 14 Y43D, Y43C,
121 14 A121fsX,
798 14 I798fsX,
44 15 C44F, C44X, C44W,