KCNH2 Variant E50Q

Summary of observed carriers, functional annotations, and structural context for KCNH2 E50Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

14%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

E50Q has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 138% of WT with a standard error of 20%. 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 (%)
-0.966 0.009 0 0.619 73

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
Literature, cohort, and gnomAD – 0 0 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 E50Q.
Neighbour residue Distance (Å) Observed variants
50 0 E50X,
47 4 G47C, G47V,
49 5 C49R, C49G,
51 6
46 6 D46Y, D46E, D46E,
53 7 G53S, G53R,
52 7 C52W,
48 7
45 8 N45D, N45K, N45K,
28 9 K28E,
100 10 R100G, R100Q, R100P,
55 11 S55L,
27 11 R27X, R27P,
54 11 Y54N, Y54X,
44 11 C44F, C44X, C44W,
26 11 S26I,
56 12 R56Q,
101 12 K101E,
129 12 F129C,
29 12 F29L, F29V, F29S, F29L, F29L,
106 12 F106L, F106V, F106L, F106L,
102 13 D102H, D102V, D102X,
130 13 E130K,
131 13 V131L, V131L, V131fsX,
104 13
59 14
30 14 I30Del, I30T
43 14 Y43D, Y43C,
23 14
108 14 C108Y,
128 14 N128S,
58 14 E58K, E58D, E58D,
741 14 K741R,
69 14 L69Del, L69P,
802 15
98 15