KCNH2 Variant A83P

Summary of observed carriers, functional annotations, and structural context for KCNH2 A83P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

19%

90% CI: 3.5% – 38.8%

1/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

A83P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 171% of WT with a standard error of 64%. 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 (%)
-2.739 0.969 -1 0.814 51

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 1 1 0
Literature, cohort, and gnomAD – 1 1 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 A83P.
Neighbour residue Distance (Å) Observed variants
83 0 A83P, A83fsX,
84 4
82 4 I82Del, I82dup, I82Ins, I82T,
80 5 A80P,
86 5 L86R,
85 5 A85P, A85V,
87 7 L87P,
79 7 A79T, A79S, A79Del, A79fsX,
65 7 T65P,
81 7 Q81E, Q81X, Q81P, Q81H, Q81H,
64 9 C64R, C64Y,
88 9
78 9 A78T, A78P,
92 9 R92C, R92L,
112 10 V112M,
77 10 R77S,
39 10 C39R, C39X,
94 10 V94L, V94L, V94A,
125 11
66 11 C66R, C66G, C66Y,
89 11 A89G, A89V,
76 11
90 11 E90K,
63 11 P63H,
110 12 V110A,
67 12
38 12
127 12
70 12 H70R, H70Q, H70Q,
96 13 I96V, I96T,
114 13 P114S,
34 13 A34T,
32 13 A32T
75 14 Q75X,
122 14
111 14 D111V,
113 14 V113Del,
40 14
91 14
74 14 T74fsX, T74M,
98 14
69 15 L69Del, L69P,
93 15 K93X, K93R,
126 15
36 15 V36X,
95 15 E95K, E95G,