KCNH2 Variant A89V

Summary of observed carriers, functional annotations, and structural context for KCNH2 A89V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

0/12 effective observations

Total carriers

2

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

A89V is present in 2 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 117% of WT with a standard error of 17%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.265 0.555 -1 0.514 13

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 – 2 1 0 –
Variant features alone – 10 10 0 –

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 A89V.
Neighbour residue Distance (Å) Observed variants
89 0 A89G, A89V,
88 3
90 4 E90K,
114 6 P114S,
85 6 A85P, A85V,
87 7 L87P,
122 7
86 7 L86R,
92 8 R92L, R92C,
116 8 K116Q,
91 9
112 9 V112M,
125 9
113 9 V113Del,
121 9 A121fsX,
115 10 V115M,
84 10
120 11
83 11 A83fsX, A83P,
123 11
34 12 A34T,
82 12 I82dup, I82Del, I82Ins, I82T,
124 12 M124R, M124T,
126 12
111 13 D111V,
117 13
81 13 Q81P, Q81H, Q81E, Q81X, Q81H,
127 13
93 14 K93R, K93X,
32 14 A32T,
39 14 C39X, C39R,
119 14 D119H, D119G,
94 14 V94L, V94L, V94A,
64 14 C64Y, C64R,
33 14 N33T,
110 14 V110A,
80 15 A80P,
35 15 R35W,