KCNH2 Variant N45H

Summary of observed carriers, functional annotations, and structural context for KCNH2 N45H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

28%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

N45H 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 (%)
-3.321 0.602 0 0.69 66

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 N45H.
Neighbour residue Distance (Å) Observed variants
45 0 N45D, N45K, N45K,
46 5 D46E, D46E, D46Y,
47 5 G47V, G47C,
44 5 C44W, C44X, C44F,
29 5 F29L, F29V, F29L, F29S, F29L
48 6
43 6 Y43D, Y43C,
49 7 C49G, C49R,
27 7 R27P, R27X,
28 7 K28E,
30 8 I30Del, I30T,
56 8 R56Q,
50 8 E50X,
19 9 I19F,
23 9
26 9 S26I,
22 10 F22S, F22Y,
31 10 I31S,
129 10 F129C,
51 10
128 10 N128S,
52 10 C52W,
800 11
798 11 I798fsX,
59 11
55 11 S55L,
801 11 K801T,
127 11
60 11 M60T,
53 11 G53S, G53R,
42 12 I42N,
41 12 V41A,
25 12 Q25P,
24 12
126 12
803 12 D803Y, D803X,
799 12 L799sp,
802 12
18 12 I18M,
54 13 Y54N, Y54X,
130 13 E130K,
57 13 A57P,
21 13
16 13 D16A,
15 13 L15V,
20 13 R20G, R20L,
32 14 A32T,
859 14 T859R, T859M,
786 14
797 14 A797T,
785 14 G785S, G785D, G785fsX,
58 14 E58D, E58K, E58D,
111 15 D111V,
17 15
66 15 C66G, C66Y, C66R,