KCNH2 Variant H485D

Summary of observed carriers, functional annotations, and structural context for KCNH2 H485D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

9%

90% CI: 0.4% – 26.8%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

H485D 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: 114% of WT with a standard error of 31%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-6.556 0.003 2 0.774 24

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 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 H485D.
Neighbour residue Distance (Å) Observed variants
485 0 H485X,
484 4
486 5
488 7 R488C, R488H,
487 7 G487S, G487R,
483 8 V483I,
399 8
489 8 I489F, I489I,
472 8 R472C, R472X,
398 9 W398L, W398X,
474 9 T474I,
473 10 T473P,
400 10 I400N,
482 11 V482A,
475 11 Y475C, Y475Del,
490 11 A490T, A490P,
401 12
471 12 F471X,
491 13 V491I,
480 14 E480V,
402 14 H402R,
492 14 H492Y,
9 14 A9T, A9V
470 14 N470D,
481 14
8 14
469 14
476 14 V476I,
477 15
493 15 Y493H, Y493C, Y493F, Y493Ins,