KCNH2 Variant L862P

Summary of observed carriers, functional annotations, and structural context for KCNH2 L862P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

24%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L862P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 2%. 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 (%)
-6.314 1.0 -3 0.967 77

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
Italy Cohort 2020 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 L862P.
Neighbour residue Distance (Å) Observed variants
862 0 L862P,
861 4 N861H, N861I,
806 5 G806R, G806R,
819 5 N819K, N819K,
807 5 E807X,
818 6 S818A, S818W, S818L,
860 6
820 7 G820R, G820R,
776 7 L776I, L776P,
863 7 R863X, R863P
805 8 F805S, F805C,
816 8 G816V,
808 9
817 9
858 9 I858V, I858T,
789 9
770 9
859 10 T859M, T859R,
773 10
774 10 D774Y, D774X,
772 10
822 10 V822M, V822L, V822L,
778 10 A778T,
791 10 R791W, R791Q,
821 10 D821E, D821E,
812 10 Y812S,
780 11
61 11 Q61R,
779 11
775 11
804 11
796 11 V796L, V796L, V796Del,
797 11 A797T,
777 12
790 12
771 12 H771fsX, H771R,
815 12
809 12
799 12 L799sp,
57 12 A57P,
60 13 M60T,
769 13
811 13
835 13 R835W, R835fsX, R835Q,
787 13
803 14 D803Y, D803X,
788 14 E788K, E788D, E788D,
781 14
857 14 E857X,
823 14 R823W, R823fsX, R823T, R823Q,
856 15
810 15
794 15 V794I, V794D,
814 15
798 15 I798fsX,
749 15
833 15
42 15 I42N,
768 15
813 15