KCNH2 Variant A85V

Summary of observed carriers, functional annotations, and structural context for KCNH2 A85V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

36%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A85V 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 6%. 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 (%)
-2.79 0.907 0 0.888 75

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
15840476 2005 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 A85V.
Neighbour residue Distance (Å) Observed variants
85 0 A85P, A85V,
86 4 L86R,
92 5 R92C, R92L,
83 5 A83P, A83fsX,
84 5
88 5
87 6 L87P,
82 6 I82Del, I82dup, I82Ins, I82T,
90 6 E90K,
89 6 A89G, A89V,
112 7 V112M,
81 8 Q81E, Q81X, Q81P, Q81H, Q81H,
125 9
80 9 A80P,
114 9 P114S,
94 9 V94L, V94L, V94A,
91 9
113 10 V113Del,
64 10 C64R, C64Y,
79 10 A79T, A79S, A79Del, A79fsX,
110 10 V110A,
65 10 T65P,
127 11
111 11 D111V,
122 11
93 11 K93X, K93R,
78 11 A78T, A78P,
39 12 C39R, C39X,
126 12
34 12 A34T,
32 13 A32T,
115 13 V115M,
77 13 R77S,
116 13 K116Q,
124 13 M124T, M124R,
66 14 C66R, C66G, C66Y,
96 14 I96V, I96T,
109 14 L109X, L109Q, L109P,
123 14
121 14 A121fsX,
63 14 P63H,
128 14 N128S,
30 14 I30Del, I30T,
33 14 N33T
38 15
95 15 E95K, E95G,
129 15 F129C,
76 15