KCNH2 Variant V795I

Summary of observed carriers, functional annotations, and structural context for KCNH2 V795I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

6%

1/19 effective observations

Total carriers

9

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

V795I is present in 9 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 114% of WT with a standard error of 10%. 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 (%)
-0.964 0.972 3 0.698 29

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
Literature, cohort, and gnomAD – 9 2 0 –
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 V795I.
Neighbour residue Distance (Å) Observed variants
795 0 V795I,
794 4 V794I, V794D,
796 4 V796L, V796L, V796Del,
790 6
797 6 A797T,
33 6 N33T
788 6 E788K, E788D, E788D,
42 6 I42N,
789 7
12 7 N12D,
798 8 I798fsX,
793 8 D793N,
124 8 M124T, M124R,
32 9 A32T,
791 9 R791W, R791Q,
15 9 L15V,
36 9 V36X,
792 9
35 9 R35W,
40 9
123 9
34 9 A34T,
31 9 I31S,
823 10 R823W, R823fsX, R823T, R823Q,
41 10 V41A,
11 10 Q11L, Q11H, Q11H,
14 10
821 11 D821E, D821E,
822 11 V822M, V822L, V822L,
39 11 C39R, C39X,
799 11 L799sp,
787 11
820 11 G820R, G820R,
43 11 Y43D, Y43C,
825 11
61 12 Q61R,
60 12 M60T,
13 12 T13N,
860 12
125 12
824 12
10 12
786 12
819 13 N819K, N819K,
37 13
122 13
16 13 D16A,
115 13 V115M,
30 14 I30Del, I30T,
18 14 I18M,
19 14 I19F,
38 14
126 14
44 14 C44F, C44X, C44W,
64 14 C64R, C64Y,
800 14
766 14
121 15 A121fsX,
859 15 T859M, T859R,
117 15
63 15 P63H,