KCNH2 Variant H70Q

Summary of observed carriers, functional annotations, and structural context for KCNH2 H70Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

30%

4/13 effective observations

Total carriers

3

1 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

H70Q has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 83% of WT with a standard error of 16%. 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 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.329 0.996 -1 0.669 70

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 3 2 1
Literature, cohort, and gnomAD – 3 2 1 –
Variant features alone – 10 7 3 –

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 H70Q.
Neighbour residue Distance (Å) Observed variants
70 0 H70R, H70Q, H70Q,
69 5 L69Del, L69P,
71 5 G71R, G71R, G71W, G71E,
67 5
74 6 T74fsX, T74M,
98 6
66 6 C66R, C66G, C66Y,
68 7 F68L, F68V, F68L, F68L,
99 7 Y99N, Y99S,
79 8 A79T, A79S, A79Del, A79fsX,
97 8
96 8 I96V, I96T,
65 8 T65P,
72 8 P72T, P72S, P72Q, P72R,
73 9 R73G, R73C, R73fsX, R73H,
75 9 Q75X,
76 10
78 10 A78T, A78P,
82 10 I82Del, I82dup, I82Ins, I82T,
106 11 F106L, F106V, F106L, F106L,
105 11
80 11 A80P,
63 11 P63H,
64 11 C64R, C64Y,
77 12 R77S,
100 12 R100G, R100Q, R100P,
108 12 C108Y,
52 12 C52W,
54 12 Y54N, Y54X,
110 12 V110A,
83 12 A83P, A83fsX,
103 12
62 13 R62Q,
94 13 V94L, V94L, V94A,
81 13 Q81E, Q81X, Q81P, Q81H, Q81H,
107 13 L107P,
104 13
95 13 E95K, E95G,
101 13 K101E,
129 13 F129C
59 14
51 14
48 14
127 14
102 15 D102H, D102V, D102X,
109 15 L109X, L109Q, L109P,
53 15 G53S, G53R,