KCNH2 Variant I82dup

Summary of observed carriers, functional annotations, and structural context for KCNH2 I82dup. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

%

NA/NA effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I82dup has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
None None None None 70

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
23098067 2012 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 NA NA –

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 I82dup.
Neighbour residue Distance (Å) Observed variants
82 0 I82Del, I82dup, I82Ins, I82T,
83 4 A83P, A83fsX,
79 5 A79T, A79S, A79Del, A79fsX,
81 5 Q81E, Q81X, Q81P, Q81H, Q81H,
80 6 A80P,
85 6 A85P, A85V,
94 6 V94L, V94L, V94A,
65 7 T65P,
78 7 A78T, A78P,
84 7
86 7 L86R,
110 7 V110A,
112 8 V112M,
92 8 R92C, R92L,
64 8 C64R, C64Y,
96 9 I96V, I96T,
66 9 C66R, C66G, C66Y,
77 9 R77S,
127 9
87 10 L87P,
70 10 H70R, H70Q, H70Q,
76 10
111 11 D111V,
125 11
98 11
95 11 E95K, E95G,
90 11 E90K,
93 11 K93X, K93R,
88 11
67 11
109 11 L109X, L109Q, L109P,
75 11 Q75X,
63 12 P63H,
129 12 F129C,
69 12 L69Del, L69P,
74 12 T74fsX, T74M,
108 12 C108Y,
89 12 A89G, A89V,
39 12 C39R, C39X,
113 12 V113Del,
97 12
91 12
114 12 P114S,
30 13 I30Del, I30T,
126 13
128 13 N128S,
32 13 A32T
68 14 F68L, F68V, F68L, F68L,
71 14 G71R, G71R, G71W, G71E,
38 14
41 15 V41A,
40 15
107 15 L107P,