KCNH2 Variant R35P

Summary of observed carriers, functional annotations, and structural context for KCNH2 R35P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

16%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R35P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 92% of WT with a standard error of 12%. 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 (%)
-2.592 0.432 -3 0.838 79

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 R35P.
Neighbour residue Distance (Å) Observed variants
35 0 R35W,
34 4 A34T,
36 4 V36X,
33 5 N33T,
794 7 V794I, V794D,
37 7
39 8 C39R, C39X,
123 8
795 9 V795I,
122 9
124 9 M124R, M124T,
40 9
38 9
32 9 A32T,
793 10 D793N,
792 10
796 10 V796L, V796Del, V796L,
125 10
121 11 A121fsX,
791 11 R791Q, R791W,
42 12 I42N,
86 12 L86R,
790 12
87 12 L87P,
41 13 V41A,
64 13 C64Y, C64R,
31 13 I31S,
115 13 V115M,
117 13
12 13 N12D,
797 14 A797T,
63 14 P63H,
120 14
116 14 K116Q,
114 14 P114S,
61 14 Q61R,
789 15
11 15 Q11H, Q11L, Q11H,
89 15 A89G, A89V,
15 15 L15V,
14 15