KCNH2 Variant I30Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 I30Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

39%

4/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I30Del has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
None None None None 88

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
24606995 2014 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 7 3 –

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 I30Del.
Neighbour residue Distance (Å) Observed variants
30 0 I30Del, I30T,
127 5
31 5 I31S,
29 5 F29L, F29V, F29S, F29L, F29L,
43 6 Y43D, Y43C,
41 7 V41A,
126 7
44 7 C44F, C44X, C44W,
48 7
32 7 A32T,
129 7 F129C,
45 8 N45D, N45K, N45K,
64 8 C64R, C64Y,
128 8 N128S,
42 8 I42N,
59 9
125 9
28 9 K28E,
66 9 C66R, C66G, C66Y,
60 10 M60T,
40 10
112 10 V112M,
47 10 G47C, G47V,
27 10 R27X, R27P,
124 10 M124T, M124R,
798 10 I798fsX,
19 10 I19F,
110 11 V110A,
111 11 D111V,
22 11 F22Y, F22S,
49 11 C49R, C49G,
56 11 R56Q,
113 11 V113Del,
65 11 T65P,
63 11 P63H,
39 11 C39R, C39X,
33 11 N33T
18 11 I18M,
52 12 C52W,
51 12
69 12 L69Del, L69P,
15 12 L15V,
62 12 R62Q,
46 12 D46Y, D46E, D46E,
797 12 A797T,
114 12 P114S,
68 12 F68L, F68V, F68L, F68L,
86 13 L86R,
796 13 V796L, V796L, V796Del,
98 13
82 13 I82Del, I82dup, I82Ins, I82T,
55 13 S55L,
61 13 Q61R,
115 13 V115M,
108 13 C108Y,
54 13 Y54N, Y54X,
130 13 E130K,
109 13 L109X, L109Q, L109P,
795 14 V795I,
34 14 A34T,
23 14
57 14 A57P,
50 14 E50X,
53 14 G53S, G53R,
58 14 E58K, E58D, E58D,
26 14 S26I,
799 14 L799sp,
123 14
25 14 Q25P,
67 14
85 14 A85P, A85V,
800 15
21 15
94 15 V94L, V94L, V94A,
36 15 V36X,
16 15 D16A,
14 15
38 15