KCNH2 Variant E519V

Summary of observed carriers, functional annotations, and structural context for KCNH2 E519V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

10%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

E519V 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: 119% of WT with a standard error of 8%. 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 (%)
-3.605 0.996 -2 0.915 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 – 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 E519V.
Neighbour residue Distance (Å) Observed variants
519 0
518 4
520 4
517 5
521 5
516 7
522 7 G522E,
515 8
523 8
514 8 G514S,
524 8
513 9
525 9 K525N, K525N,
512 10
526 10
511 11
527 11
510 11
528 11 R528X, R528P, R528W,
509 12 D509N,
529 12
508 13
530 13
507 13 P507S, P507L,
531 13 R531Del, R531Q, R531W,
506 14 I506V,
532 14
505 14 A505V,
533 14
504 15 A504V,
534 15 R534C,