KCNH2 Variant V36G

Summary of observed carriers, functional annotations, and structural context for KCNH2 V36G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

12%

90% CI: 1.5% – 33.9%

1/11 effective observations

Total carriers

1

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

V36G is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 84% of WT with a standard error of 14%. 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 (%)
-3.749 0.216 -4 0.762 55

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 – 1 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 V36G.
Neighbour residue Distance (Å) Observed variants
36 0 V36X,
35 4 R35W,
37 5
34 5 A34T,
33 5 N33T
39 5 C39R, C39X,
40 6
38 6
794 7 V794I, V794D,
32 8 A32T,
796 8 V796L, V796L, V796Del,
795 9 V795I,
791 9 R791W, R791Q,
124 10 M124T, M124R,
41 10 V41A,
123 10
42 10 I42N,
63 10 P63H,
125 10
64 11 C64R, C64Y,
792 11
61 11 Q61R,
122 11
793 12 D793N,
86 12 L86R,
797 12 A797T,
790 12
31 12 I31S,
87 13 L87P,
62 13 R62Q,
60 13 M60T,
789 13
65 13 T65P,
121 14 A121fsX,
819 14 N819K, N819K,
798 15 I798fsX,
30 15 I30Del, I30T,
788 15 E788K, E788D, E788D,
12 15 N12D,
115 15 V115M,
83 15 A83P, A83fsX,