KCNH2 Variant A32T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A32T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

35%

90% CI: 14.1% – 59.3%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A32T has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 35% of WT with a standard error of 19%. 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 (%)
-2.454 1.0 -1 0.827 79

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
26496715 2015 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 A32T.
Neighbour residue Distance (Å) Observed variants
32 0 A32T,
31 4 I31S,
33 5 N33T
125 5
124 5 M124T, M124R,
40 5
41 6 V41A,
42 6 I42N,
39 6 C39R, C39X,
64 7 C64R, C64Y,
34 7 A34T,
30 7 I30Del, I30T,
126 8
127 8
36 8 V36X,
123 8
795 9 V795I,
796 9 V796L, V796L, V796Del,
63 9 P63H,
86 9 L86R,
35 9 R35W,
43 9 Y43D, Y43C,
122 10
115 10 V115M,
114 10 P114S,
797 10 A797T,
798 10 I798fsX,
60 10 M60T,
15 10 L15V,
38 10
29 11 F29L, F29V, F29S, F29L, F29L,
65 11 T65P,
113 11 V113Del,
112 11 V112M,
44 11 C44F, C44X, C44W,
794 11 V794I, V794D,
61 11 Q61R,
66 11 C66R, C66G, C66Y,
59 12
62 12 R62Q,
14 12
18 12 I18M,
37 12
85 13 A85P, A85V,
788 13 E788K, E788D, E788D,
19 13 I19F,
128 13 N128S,
12 13 N12D,
87 13 L87P,
82 13 I82Del, I82dup, I82Ins, I82T,
83 13 A83P, A83fsX,
116 13 K116Q,
48 13
121 13 A121fsX,
129 13 F129C,
789 13
111 14 D111V,
45 14 N45D, N45K, N45K,
89 14 A89G, A89V,
790 14
110 14 V110A,
56 14 R56Q,
90 14 E90K,
22 14 F22Y, F22S,
791 14 R791W, R791Q,
799 14 L799sp,
88 15
860 15