KCNH2 Variant T13N

Summary of observed carriers, functional annotations, and structural context for KCNH2 T13N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

3%

90% CI: 1.2% – 13.7%

2/42 effective observations

Total carriers

32

1 LQT2 · 24 unaffected

Functional studies

0

Publications with functional data

T13N is present in 28 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 96% of WT with a standard error of 38%. 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 (%)
-2.764 0.135 -1 0.897 9

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
France Cohort 2020 4 3 1
Literature, cohort, and gnomAD – 32 24 1 –
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 T13N.
Neighbour residue Distance (Å) Observed variants
13 0 T13N,
10 5
14 5
12 5 N12D,
825 6
16 6 D16A,
15 6 L15V,
9 6 A9T, A9V,
17 7
11 7 Q11L, Q11H, Q11H,
826 9 T826A, T826I,
788 9 E788K, E788D, E788D,
18 9 I18M,
786 9
824 10
765 10
8 10
19 10 I19F,
766 11
20 11 R20G, R20L,
798 11 I798fsX,
7 12
795 12 V795I,
823 12 R823W, R823fsX, R823T, R823Q,
480 12 E480V,
787 12
482 12 V482A,
785 12 G785S, G785fsX, G785D,
481 12
827 12
124 12 M124T, M124R,
828 13
123 13
21 13
797 13 A797T,
115 13 V115M,
479 13
764 13
790 14
31 14 I31S
117 14
767 14 D767X,
43 14 Y43D, Y43C,
42 14 I42N,
483 14 V483I,
799 14 L799sp,
800 14
789 14
6 15 G6R,
763 15
488 15 R488C, R488H,
793 15 D793N,
484 15
22 15 F22Y, F22S,
794 15 V794I, V794D,