KCNH2 Variant E519Q
Summary of observed carriers, functional annotations, and structural context for KCNH2 E519Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
10%
1/10 effective observations
Total carriers
0
0 LQT2 · 0 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 158% of WT with a standard error of 28%. 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
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT2 (%) |
|---|---|---|---|---|
| -2.147 | 0.756 | 1 | 0.75 | 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
| 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.
| 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 | P507L, P507S, |
| 531 | 13 | R531Q, R531Del, R531W, |
| 506 | 14 | I506V, |
| 532 | 14 | |
| 505 | 14 | A505V, |
| 533 | 14 | |
| 504 | 15 | A504V, |
| 534 | 15 | R534C, |