KCNH2 Variant E444A
Summary of observed carriers, functional annotations, and structural context for KCNH2 E444A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
15%
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: 131% of WT with a standard error of 22%. 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 (%) |
|---|---|---|---|---|
| -1.936 | 0.0 | -1 | 0.482 | 41 |
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 |
|---|---|---|
| 444 | 0 | E444K, E444D, E444D, |
| 443 | 4 | T443fsX, T443N, |
| 445 | 4 | |
| 442 | 5 | |
| 446 | 5 | |
| 441 | 7 | P441R, P441L, |
| 447 | 7 | Y447X, |
| 440 | 8 | P440L, |
| 448 | 8 | A448T, A448S, |
| 439 | 8 | |
| 449 | 8 | |
| 438 | 9 | E438K, E438X, |
| 450 | 9 | |
| 437 | 10 | |
| 451 | 10 | P451L, |
| 436 | 11 | T436M, |
| 452 | 11 | |
| 435 | 11 | E435G, E435X, |
| 453 | 11 | |
| 434 | 12 | |
| 454 | 12 | |
| 433 | 13 | |
| 455 | 13 | |
| 432 | 13 | |
| 456 | 13 | D456Y, |
| 431 | 14 | F431L, F431L, F431L, |
| 457 | 14 | L457P |
| 430 | 14 | |
| 458 | 14 | |
| 429 | 15 | A429P, A429V, |
| 459 | 15 |