KCNH2 Variant V483F

Summary of observed carriers, functional annotations, and structural context for KCNH2 V483F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

19%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

V483F 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: 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 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-4.633 0.998 -1 0.905 34

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 V483F.
Neighbour residue Distance (Å) Observed variants
483 0 V483I,
484 4
482 4 V482A,
475 5 Y475Del, Y475C,
474 6 T474I,
488 6 R488C, R488H,
480 7 E480V,
489 7 I489F, I489I,
481 7
476 7 V476I,
477 7
485 8 H485X,
473 9 T473P,
402 9 H402R,
492 10 H492Y,
6 10 G6R,
487 10 G487R, G487S,
486 10
8 10
401 10
9 10 A9T, A9V,
478 10 A478D,
479 11
490 11 A490T, A490P,
491 11 V491I,
400 11 I400N,
399 12
403 12
472 12 R472C, R472X,
7 12
5 12
4 12
471 13 F471X,
470 13 N470D,
493 13 Y493C, Y493F, Y493Ins, Y493H,
10 14
13 14 T13N,
398 14 W398X, W398L,
765 14
827 15
404 15
3 15
469 15