KCNH2 Variant H396Q
Summary of observed carriers, functional annotations, and structural context for KCNH2 H396Q. 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: 93% of WT with a standard error of 13%. 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 (%) |
|---|---|---|---|---|
| -6.058 | 0.125 | 0 | 0.702 | 8 |
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 |
|---|---|---|
| 396 | 0 | |
| 395 | 4 | |
| 397 | 4 | R397X, R397H |
| 394 | 5 | R394C, R394H, |
| 398 | 5 | W398X, W398L, |
| 393 | 7 | P393L, |
| 399 | 7 | |
| 392 | 8 | |
| 400 | 8 | I400N, |
| 391 | 8 | Q391X, |
| 401 | 8 | |
| 390 | 9 | |
| 402 | 9 | H402R, |
| 389 | 10 | |
| 403 | 10 | |
| 388 | 11 | |
| 404 | 11 | |
| 387 | 11 | |
| 405 | 11 | |
| 386 | 12 | P386X, |
| 406 | 12 | |
| 385 | 13 | |
| 407 | 13 | |
| 384 | 13 | |
| 408 | 13 | |
| 383 | 14 | |
| 409 | 14 | V409M, V409L, V409L, |
| 382 | 14 | A382T, |
| 410 | 14 | W410X, |
| 381 | 15 | |
| 411 | 15 |