KCNH2 Variant N38T

Summary of observed carriers, functional annotations, and structural context for KCNH2 N38T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

15%

90% CI: 2.0% – 36.3%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

N38T has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 74% of WT with a standard error of 16%. 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 (%)
-3.582 0.008 -1 0.691 38

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 N38T.
Neighbour residue Distance (Å) Observed variants
38 0
37 5
39 5 C39R, C39X,
36 6 V36X,
63 6 P63H,
40 7
64 8 C64R, C64Y,
34 9 A34T,
65 9 T65P,
35 9 R35W,
33 10 N33T
62 10 R62Q,
41 10 V41A,
32 10 A32T,
61 10 Q61R,
86 11 L86R,
66 12 C66R, C66G, C66Y,
67 12
83 12 A83P, A83fsX,
125 12
796 12 V796L, V796L, V796Del,
87 12 L87P,
42 13 I42N,
794 13 V794I, V794D,
791 13 R791W, R791Q,
60 13 M60T,
124 14 M124T, M124R,
795 14 V795I,
59 14
82 14 I82Del, I82dup, I82Ins, I82T,
31 14 I31S,
68 14 F68L, F68V, F68L, F68L,
122 15
85 15 A85P, A85V,
123 15
30 15 I30Del, I30T,