KCNH2 Variant K93R

Summary of observed carriers, functional annotations, and structural context for KCNH2 K93R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

1%

90% CI: 0.1% – 5.8%

0/143 effective observations

Total carriers

133

0 LQT2 · 39 unaffected

Functional studies

0

Publications with functional data

K93R is present in 133 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 124% of WT with a standard error of 9%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-1.618 0.031 2 0.441 28

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 – 133 39 0 –
Variant features alone – 10 10 0 –

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 K93R.
Neighbour residue Distance (Å) Observed variants
93 0 K93X, K93R,
111 5 D111V,
94 6 V94L, V94L, V94A,
109 6 L109X, L109Q, L109P,
91 6
110 7 V110A,
92 7 R92C, R92L,
112 7 V112M,
95 8 E95K, E95G,
128 9 N128S,
113 10 V113Del,
90 10 E90K,
108 10 C108Y,
130 11 E130K,
129 11 F129C,
81 11 Q81E, Q81X, Q81P, Q81H, Q81H,
127 11
82 11 I82Del, I82dup, I82Ins, I82T,
85 11 A85P, A85V,
96 12 I96V, I96T,
114 12 P114S,
126 12
131 12 V131L, V131L, V131fsX,
78 13 A78T, A78P,
107 13 L107P,
89 14 A89G, A89V,
28 14 K28E
86 14 L86R,
79 14 A79T, A79S, A79Del, A79fsX,
84 14
98 15
83 15 A83P, A83fsX,
80 15 A80P,
125 15
88 15
97 15