KCNH2 Variant E37V

Summary of observed carriers, functional annotations, and structural context for KCNH2 E37V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

14%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

E37V has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 83% 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 (%)
-3.594 0.004 -3 0.578 47

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 E37V.
Neighbour residue Distance (Å) Observed variants
37 0
38 5
36 5 V36X,
35 7 R35W,
39 7 C39R, C39X,
34 9 A34T,
40 9
33 10 N33T,
63 11 P63H,
794 11 V794I, V794D,
791 11 R791W, R791Q,
796 12 V796L, V796Del, V796L,
61 12 Q61R,
64 12 C64R, C64Y,
32 12 A32T,
41 13 V41A,
792 13
795 13 V795I,
62 13 R62Q,
86 13 L86R,
87 14 L87P,
65 14 T65P,
125 14
42 14 I42N,
123 14
124 14 M124R, M124T,
122 15
793 15 D793N,
819 15 N819K, N819K,