KCNH2 Variant L69Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 L69Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

34%

90% CI: 19.0% – 60.4%

5/14 effective observations

Total carriers

4

2 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

L69Del has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

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 (%)
None None None None 78

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 4 2 2
Literature, cohort, and gnomAD – 4 2 2 –
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 L69Del.
Neighbour residue Distance (Å) Observed variants
69 0 L69Del, L69P,
68 4 F68L, F68V, F68L, F68L,
70 5 H70R, H70Q, H70Q,
98 5
66 5 C66R, C66G, C66Y,
67 7
99 7 Y99N, Y99S,
52 7 C52W,
71 8 G71R, G71R, G71W, G71E,
54 8 Y54N, Y54X,
97 8
100 8 R100G, R100Q, R100P,
65 9 T65P,
106 9 F106L, F106V, F106L, F106L,
96 9 I96V, I96T,
74 9 T74fsX, T74M,
48 9
51 10
101 10 K101E,
59 10
53 10 G53S, G53R,
105 10
108 10 C108Y,
63 10 P63H,
62 11 R62Q,
129 11 F129C,
64 11 C64R, C64Y,
103 11
104 11
72 11 P72T, P72S, P72Q, P72R,
79 11 A79T, A79S, A79Del, A79fsX,
73 11 R73G, R73C, R73fsX, R73H,
58 11 E58K, E58D, E58D,
110 12 V110A,
30 12 I30Del, I30T
102 12 D102H, D102V, D102X,
82 12 I82Del, I82dup, I82Ins, I82T,
49 12 C49R, C49G,
127 12
107 12 L107P,
55 13 S55L,
78 13 A78T, A78P,
75 13 Q75X,
41 13 V41A,
28 13 K28E,
109 14 L109X, L109Q, L109P,
94 14 V94L, V94L, V94A,
44 14 C44F, C44X, C44W,
47 14 G47C, G47V,
95 14 E95K, E95G,
76 14
60 14 M60T,
50 14 E50X,
80 15 A80P,
83 15 A83P, A83fsX,
128 15 N128S,
57 15 A57P,
131 15 V131L, V131L, V131fsX,
29 15 F29L, F29V, F29S, F29L, F29L,