KCNH2 Variant L87P

Summary of observed carriers, functional annotations, and structural context for KCNH2 L87P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

37%

90% CI: 15.5% – 61.4%

4/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L87P 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 0%. 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 (%)
-3.585 0.913 -3 0.849 84

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
12402336 2002 1 0 1
Literature, cohort, and gnomAD – 1 0 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 L87P.
Neighbour residue Distance (Å) Observed variants
87 0 L87P,
88 5
86 5 L86R,
85 6 A85P, A85V,
84 7
83 7 A83P, A83fsX,
89 7 A89G, A89V,
122 9
90 9 E90K,
125 10
34 10 A34T,
82 10 I82Del, I82dup, I82Ins, I82T,
39 10 C39R, C39X,
92 10 R92C, R92L,
114 11 P114S,
80 11 A80P,
64 12 C64R, C64Y,
112 12 V112M,
81 12 Q81E, Q81X, Q81P, Q81H, Q81H,
121 12 A121fsX,
65 12 T65P,
38 12
35 12 R35W,
123 13
36 13 V36X,
32 13 A32T,
33 13 N33T
116 13 K116Q,
79 13 A79T, A79S, A79Del, A79fsX,
124 14 M124T, M124R,
113 14 V113Del,
37 14
115 14 V115M,
120 14
91 14
63 14 P63H,
127 15
40 15
94 15 V94L, V94L, V94A,
126 15