KCNH2 Variant I19F

Summary of observed carriers, functional annotations, and structural context for KCNH2 I19F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

18%

2/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I19F has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 33% of WT with a standard error of 12%. 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 (%)
-2.334 0.396 -1 0.795 73

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
France Cohort 2020 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 I19F.
Neighbour residue Distance (Å) Observed variants
19 0 I19F,
18 5 I18M,
16 5 D16A,
17 6
22 6 F22Y, F22S,
15 7 L15V,
23 7
20 7 R20G, R20L,
43 7 Y43D, Y43C,
29 7 F29L, F29V, F29S, F29L, F29L,
21 7
798 8 I798fsX,
45 9 N45D, N45K, N45K,
31 9 I31S,
786 9
27 10 R27X, R27P,
14 10
24 10
126 10
800 10
25 10 Q25P,
44 10 C44F, C44X, C44W,
785 10 G785S, G785fsX, G785D,
13 10 T13N,
30 10 I30Del, I30T,
801 11 K801T,
42 11 I42N,
825 11
26 11 S26I,
46 12 D46Y, D46E, D46E,
788 12 E788K, E788D, E788D,
799 12 L799sp,
826 12 T826A, T826I,
128 12 N128S,
124 12 M124T, M124R,
12 12 N12D,
797 12 A797T,
47 13 G47C, G47V,
787 13
28 13 K28E,
127 13
32 13 A32T
56 13 R56Q,
115 13 V115M,
48 13
113 14 V113Del,
41 14 V41A,
795 14 V795I,
803 14 D803Y, D803X,
828 14
129 14 F129C,
125 14
824 15
60 15 M60T,
802 15
784 15 R784G, R784W, R784Q,
10 15
49 15 C49R, C49G,