KCNH2 Variant P114S

Summary of observed carriers, functional annotations, and structural context for KCNH2 P114S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

16%

12/29 effective observations

Total carriers

19

11 LQT2 · 8 unaffected

Functional studies

0

Publications with functional data

P114S 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 3%. 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 (%)
-6.243 0.876 -2 0.963 45

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
Japan Cohort 2020 8 2 6
France Cohort 2020 10 5 5
16922724 2006 1 1
Literature, cohort, and gnomAD – 19 8 11 –
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 P114S.
Neighbour residue Distance (Å) Observed variants
114 0 P114S,
113 4 V113Del,
115 5 V115M,
125 6
90 6 E90K,
89 6 A89G, A89V,
112 6 V112M,
116 6 K116Q,
126 6
122 7
91 8
124 8 M124T, M124R,
86 8 L86R,
123 9
85 9 A85P, A85V,
88 9
111 9 D111V,
127 9
92 9 R92C, R92L,
121 9 A121fsX,
32 10 A32T,
34 11 A34T,
117 11
31 11 I31S,
87 11 L87P,
120 11
128 12 N128S,
33 12 N33T
18 12 I18M,
93 12 K93X, K93R,
30 12 I30Del, I30T,
110 12 V110A,
64 12 C64R, C64Y,
82 12 I82Del, I82dup, I82Ins, I82T,
39 13 C39R, C39X,
14 13
83 13 A83P, A83fsX,
15 13 L15V,
29 13 F29L, F29V, F29S, F29L, F29L,
22 13 F22Y, F22S,
94 14 V94L, V94L, V94A,
84 14
118 14 E118K, E118X, E118D, E118D,
119 14 D119H, D119G,
35 14 R35W,
129 14 F129C,
42 15 I42N,
40 15
65 15 T65P,