KCNH2 Variant L1023Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 L1023Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

6%

0/14 effective observations

Total carriers

4

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

L1023Del is present in 3 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

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 (%)
None None None None 0

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
14661677 2003 1 1
Literature, cohort, and gnomAD – 4 1 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 L1023Del.
Neighbour residue Distance (Å) Observed variants
1023 0 L1023P, L1023Del,
1022 4
1024 4
1021 5 S1021N, S1021fsX,
1025 5
1020 7
1026 7 P1026R,
1019 8
1027 8 L1027I,
1018 8 P1018A, P1018L,
1028 8 S1028Del,
1017 9 A1017V, A1017T, A1017fsX, A1017S,
1029 9 S1029fsX,
1016 10
1030 10 P1030X, P1030L,
1015 11 C1015Y,
1031 11 G1031X, G1031fsX, G1031C,
1014 11 R1014fsX, R1014X,
1032 11 R1032W, R1032P, R1032Q, R1032fsX, R1032X,
1013 12
1033 12 R1033fsX, R1033X, R1033W, R1033Q,
1012 13 L1012fsX,
1034 13 P1034X, P1034fsX,
1011 13 E1011K,
1035 13 R1035fsX, R1035Q, R1035X, R1035W
1010 14
1036 14 G1036Del, G1036X, G1036fsX, G1036D,
1009 14 Y1009X,
1037 14 D1037N, D1037E, D1037E, D1037fsX, D1037X,
1008 15
1038 15 V1038X, V1038M, V1038L, V1038fsX, V1038L,