KCNH2 Variant A360E
Summary of observed carriers, functional annotations, and structural context for KCNH2 A360E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
10%
1/11 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: 79% of WT with a standard error of 38%. 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 (%) |
|---|---|---|---|---|
| -3.4 | 0.609 | -1 | 0.767 | 5 |
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 | 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 |
|---|---|---|
| 360 | 0 | |
| 359 | 4 | I359V, |
| 361 | 4 | |
| 358 | 5 | |
| 362 | 5 | |
| 357 | 7 | E357D, E357D, |
| 363 | 7 | I363X, |
| 356 | 8 | R356C, R356H, |
| 364 | 8 | K364X, |
| 355 | 8 | D355G, |
| 365 | 8 | E365G, |
| 354 | 9 | |
| 366 | 9 | R366X, R366Q, |
| 353 | 10 | T353S, T353S, |
| 367 | 10 | T367S, T367S, |
| 352 | 11 | |
| 368 | 11 | H368Y, |
| 351 | 11 | S351L, |
| 369 | 11 | N369K, N369K |
| 350 | 12 | |
| 370 | 12 | |
| 349 | 13 | |
| 371 | 13 | |
| 348 | 13 | |
| 372 | 13 | |
| 347 | 14 | P347S, |
| 373 | 14 | |
| 346 | 14 | D346N, D346Y, D346E, D346E, |
| 374 | 14 | |
| 345 | 15 | G345S, |
| 375 | 15 |