KCNH2 Variant H396N

Summary of observed carriers, functional annotations, and structural context for KCNH2 H396N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

10%

90% CI: 0.6% – 28.8%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

H396N has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 62% of WT with a standard error of 14%. 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 (%)
-4.98 0.02 2 0.634 8

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 H396N.
Neighbour residue Distance (Å) Observed variants
396 0
395 4
397 4 R397X, R397H,
394 5 R394C, R394H,
398 5 W398L, W398X,
393 7 P393L,
399 7
392 8
400 8 I400N,
391 8 Q391X,
401 8
390 9
402 9 H402R,
389 10
403 10
388 11
404 11
387 11
405 11
386 12 P386X,
406 12
385 13
407 13
384 13
408 13
383 14
409 14 V409M, V409L, V409L,
382 14 A382T,
410 14 W410X
381 15
411 15