KCNH2 Variant H402R

Summary of observed carriers, functional annotations, and structural context for KCNH2 H402R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

42%

10/18 effective observations

Total carriers

8

8 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

H402R 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 0%. 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 (%)
-7.603 0.691 0 0.963 86

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
Japan Cohort 2020 3 0 3
France Cohort 2020 2 0 2
19136169 2010 2 0 2
29622001 2018 1 0 1
Literature, cohort, and gnomAD – 8 0 8 –
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 H402R.
Neighbour residue Distance (Å) Observed variants
402 0 H402R,
403 5
474 5 T474I,
401 5
404 7
476 7 V476I,
5 7
3 7
473 7 T473P,
407 7
475 8 Y475C, Y475Del,
400 9 I400N,
6 9 G6R,
541 9 R541C, R541H,
482 9 V482A,
4 9
408 9
483 9 V483I,
405 10
481 10
484 11
411 11
538 11
470 11 N470D,
406 11
540 12 D540fsX,
399 12
469 12
477 12
489 12 I489F, I489I,
480 12 E480V,
8 12
537 13 R537W,
7 13
409 13 V409M, V409L, V409L,
410 13 W410X,
695 13
472 13 R472C, R472X,
492 13 H492Y,
698 13 E698K, E698X,
544 13 E544A, E544fsX,
702 14
699 14 E699D, E699D
542 14
478 14 A478D,
485 14 H485X,
471 14 F471X,
466 14 D466E, D466E,
493 14 Y493H, Y493C, Y493F, Y493Ins,
412 15 W412X,
539 15