KCNH2 Variant E372Q
Summary of observed carriers, functional annotations, and structural context for KCNH2 E372Q. 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: 112% of WT with a standard error of 15%. 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 (%) |
|---|---|---|---|---|
| -2.36 | 0.984 | 1 | 0.833 | 6 |
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 |
|---|---|---|
| 372 | 0 | |
| 371 | 4 | |
| 373 | 4 | |
| 370 | 5 | |
| 374 | 5 | |
| 369 | 7 | N369K, N369K, |
| 375 | 7 | |
| 368 | 8 | H368Y, |
| 376 | 8 | Q376sp, Q376R, |
| 367 | 8 | T367S, T367S, |
| 377 | 8 | |
| 366 | 9 | R366X, R366Q, |
| 378 | 9 | |
| 365 | 10 | E365G, |
| 379 | 10 | S379Y, |
| 364 | 11 | K364X, |
| 380 | 11 | L380X, |
| 363 | 11 | I363X, |
| 381 | 11 | |
| 362 | 12 | |
| 382 | 12 | A382T, |
| 361 | 13 | |
| 383 | 13 | |
| 360 | 13 | |
| 384 | 13 | |
| 359 | 14 | I359V, |
| 385 | 14 | |
| 358 | 14 | |
| 386 | 14 | P386X |
| 357 | 15 | E357D, E357D, |
| 387 | 15 |