KCNH2 Variant K344E
Summary of observed carriers, functional annotations, and structural context for KCNH2 K344E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
9%
0/11 effective observations
Total carriers
1
0 LQT2 · 0 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 112% 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 0 individuals with LQT2 and 10 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT2 (%) |
|---|---|---|---|---|
| -1.42 | 0.949 | 0 | 0.708 | 1 |
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 | – | 1 | 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 344 | 0 | |
| 343 | 4 | L343fsX, |
| 345 | 4 | G345S, |
| 342 | 5 | D342A, D342V, D342X, |
| 346 | 5 | D346N, D346Y, D346E, D346E, |
| 341 | 7 | |
| 347 | 7 | P347S, |
| 340 | 8 | F340L, F340L, F340L, |
| 348 | 8 | |
| 339 | 8 | |
| 349 | 8 | |
| 338 | 9 | |
| 350 | 9 | |
| 337 | 10 | T337S, T337X, T337S, |
| 351 | 10 | S351L, |
| 336 | 11 | |
| 352 | 11 | |
| 335 | 11 | Q335X, |
| 353 | 11 | T353S, T353S, |
| 334 | 12 | P334L, |
| 354 | 12 | |
| 333 | 13 | |
| 355 | 13 | D355G, |
| 332 | 13 | |
| 356 | 13 | R356C, R356H, |
| 331 | 14 | S331N, S331T |
| 357 | 14 | E357D, E357D, |
| 330 | 14 | I330V, |
| 358 | 14 | |
| 329 | 15 | |
| 359 | 15 | I359V, |