KCNH2 Variant Y327H
Summary of observed carriers, functional annotations, and structural context for KCNH2 Y327H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
6%
90% CI: 0.5% – 25.7%
0/17 effective observations
Total carriers
7
0 LQT2 · 1 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 71% 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 (%) |
|---|---|---|---|---|
| -3.167 | 0.353 | 0 | 0.606 | 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 | – | 7 | 1 | 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 |
|---|---|---|
| 327 | 0 | Y327H, |
| 326 | 4 | R326C, R326fsX, R326H, |
| 328 | 4 | R328C, R328fsX, R328H, |
| 325 | 5 | V325M, |
| 329 | 5 | |
| 324 | 7 | L324L, |
| 330 | 7 | I330V, |
| 323 | 8 | D323N, D323E, D323E, |
| 331 | 8 | S331N, S331T |
| 322 | 8 | |
| 332 | 8 | |
| 321 | 9 | D321Y, |
| 333 | 9 | |
| 320 | 10 | S320X, S320W, S320L, |
| 334 | 10 | P334L, |
| 319 | 11 | T319T, |
| 335 | 11 | Q335X, |
| 318 | 11 | |
| 336 | 11 | |
| 317 | 12 | N317S, |
| 337 | 12 | T337S, T337X, T337S, |
| 316 | 13 | |
| 338 | 13 | |
| 315 | 13 | |
| 339 | 13 | |
| 314 | 14 | G314S, |
| 340 | 14 | F340L, F340L, F340L, |
| 313 | 14 | |
| 341 | 14 | |
| 312 | 15 | R312C, R312Del, R312H, |
| 342 | 15 | D342A, D342V, D342X, |