KCNH2 Variant I489V

Summary of observed carriers, functional annotations, and structural context for KCNH2 I489V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

18%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I489V has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 65% of WT with a standard error of 21%. 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 (%)
-0.927 0.999 3 0.852 73

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 I489V.
Neighbour residue Distance (Å) Observed variants
489 0 I489F, I489I,
490 4 A490T, A490P,
486 6
487 6 G487S, G487R,
475 6 Y475C, Y475Del,
492 6 H492Y,
491 6 V491I,
488 6 R488C, R488H,
471 7 F471X,
483 7 V483I,
484 7
473 7 T473P,
493 7 Y493H, Y493C, Y493F, Y493Ins,
474 7 T474I,
485 8 H485X,
472 8 R472C, R472X,
470 9 N470D,
494 9 F494Del,
477 11
476 11 V476I,
482 11 V482A,
400 11 I400N,
469 11
399 12
498 12
402 12 H402R,
480 12 E480V,
468 12 L468F, L468X, L468R,
496 12
467 12
401 12
398 13 W398L, W398X,
495 13 K495X,
481 13
497 14 W497L, W497X,
466 14 D466E, D466E,
537 14 R537W
478 14 A478D,
407 15