KCNH2 Variant R27P

Summary of observed carriers, functional annotations, and structural context for KCNH2 R27P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

19%

90% CI: 8.4% – 50.1%

2/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R27P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 32% of WT with a standard error of 15%. 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 (%)
-3.467 0.974 -3 0.871 80

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 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 R27P.
Neighbour residue Distance (Å) Observed variants
27 0 R27X, R27P,
26 4 S26I,
28 5 K28E,
25 6 Q25P,
22 6 F22Y, F22S,
29 6 F29L, F29V, F29S, F29L, F29L,
23 6
128 7 N128S,
47 7 G47C, G47V,
45 7 N45D, N45K, N45K,
24 7
129 8 F129C,
130 8 E130K,
48 9
19 10 I19F,
21 10
46 10 D46Y, D46E, D46E,
30 10 I30Del, I30T,
50 11 E50X,
127 11
43 11 Y43D, Y43C,
126 11
51 11
18 11 I18M,
111 11 D111V,
44 12 C44F, C44X, C44W,
49 12 C49R, C49G,
131 12 V131L, V131L, V131fsX,
31 12 I31S
109 13 L109X, L109Q, L109P,
20 13 R20G, R20L,
108 13 C108Y,
110 13 V110A,
113 13 V113Del,
52 14 C52W,
17 14
112 14 V112M,
16 15 D16A,
56 15 R56Q,