KCNH2 Variant Q61R

Summary of observed carriers, functional annotations, and structural context for KCNH2 Q61R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

34%

90% CI: 13.6% – 58.6%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

Q61R has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 121% of WT with a standard error of 13%. 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.722 0.127 1 0.839 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
23098067 2012 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 10 8 2 –

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 Q61R.
Neighbour residue Distance (Å) Observed variants
61 0 Q61R,
60 5 M60T,
62 6 R62Q,
860 7
40 7
41 7 V41A,
796 7 V796L, V796L, V796Del,
59 8
57 8 A57P,
42 8 I42N,
63 9 P63H,
861 9 N861H, N861I,
797 9 A797T,
859 9 T859M, T859R,
58 10 E58K, E58D, E58D,
789 10
791 10 R791W, R791Q,
38 10
819 10 N819K, N819K,
862 11 L862P,
39 11 C39R, C39X,
56 11 R56Q,
36 11 V36X,
44 11 C44F, C44X, C44W,
32 11 A32T,
858 12 I858V, I858T,
33 12 N33T
798 12 I798fsX,
64 12 C64R, C64Y,
795 12 V795I,
55 12 S55L,
37 12
799 12 L799sp,
863 12 R863X, R863P,
31 12 I31S,
794 12 V794I, V794D,
43 13 Y43D, Y43C,
68 13 F68L, F68V, F68L, F68L,
66 13 C66R, C66G, C66Y,
820 13 G820R, G820R,
806 13 G806R, G806R,
790 13
30 13 I30Del, I30T,
805 14 F805S, F805C,
857 14 E857X,
65 14 T65P,
54 14 Y54N, Y54X,
788 14 E788K, E788D, E788D,
67 14
804 14
807 14 E807X,
35 14 R35W,
34 14 A34T,
803 14 D803Y, D803X,
818 15 S818A, S818W, S818L,