KCNH2 Variant R394S
Summary of observed carriers, functional annotations, and structural context for KCNH2 R394S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
9%
0/10 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: 101% of WT with a standard error of 10%. 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 (%) |
|---|---|---|---|---|
| -5.127 | 0.977 | -1 | 0.834 | 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 | – | 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 394 | 0 | R394C, R394H, |
| 393 | 4 | P393L, |
| 395 | 4 | |
| 392 | 5 | |
| 396 | 5 | |
| 391 | 7 | Q391X, |
| 397 | 7 | R397X, R397H, |
| 390 | 8 | |
| 398 | 8 | W398X, W398L, |
| 389 | 8 | |
| 399 | 8 | |
| 388 | 9 | |
| 400 | 9 | I400N, |
| 387 | 10 | |
| 401 | 10 | |
| 386 | 11 | P386X, |
| 402 | 11 | H402R |
| 385 | 11 | |
| 403 | 11 | |
| 384 | 12 | |
| 404 | 12 | |
| 383 | 13 | |
| 405 | 13 | |
| 382 | 13 | A382T, |
| 406 | 13 | |
| 381 | 14 | |
| 407 | 14 | |
| 380 | 14 | L380X, |
| 408 | 14 | |
| 379 | 15 | S379Y, |
| 409 | 15 | V409M, V409L, V409L, |