KCNH2 Variant G487A

Summary of observed carriers, functional annotations, and structural context for KCNH2 G487A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

0/11 effective observations

Total carriers

1

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

G487A is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 119% of WT with a standard error of 24%. 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 (%)
-1.222 0.043 2 0.537 12

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 – 1 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 G487A.
Neighbour residue Distance (Å) Observed variants
487 0 G487S, G487R,
486 4
488 5 R488C, R488H,
489 6 I489F, I489I,
490 6 A490T, A490P,
491 7 V491I,
485 7 H485X,
484 8
483 10 V483I,
471 10 F471X,
472 10 R472C, R472X,
492 10 H492Y,
494 11 F494Del
475 11 Y475C, Y475Del,
493 12 Y493H, Y493C, Y493F, Y493Ins,
473 12 T473P,
474 12 T474I,
399 13
398 13 W398L, W398X,
482 14 V482A,
470 14 N470D,
477 14
480 14 E480V,
400 15 I400N,