KCNH2 Variant N477I
Summary of observed carriers, functional annotations, and structural context for KCNH2 N477I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
23%
90% CI: 5.6% – 46.7%
2/10 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: 102% of WT with a standard error of 8%. 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 2 individuals with LQT2 and 8 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT2 (%) |
|---|---|---|---|---|
| -8.298 | 0.997 | -4 | 0.918 | 48 |
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 | 8 | 2 | – |
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 |
|---|---|---|
| 477 | 0 | |
| 478 | 4 | A478D, |
| 480 | 4 | E480V, |
| 476 | 5 | V476I, |
| 479 | 5 | |
| 475 | 6 | Y475C, Y475Del, |
| 481 | 6 | |
| 483 | 7 | V483I, |
| 482 | 8 | V482A, |
| 492 | 8 | H492Y, |
| 4 | 9 | |
| 6 | 10 | G6R, |
| 488 | 10 | R488C, R488H, |
| 827 | 10 | |
| 474 | 11 | T474I, |
| 489 | 11 | I489F, I489I, |
| 484 | 11 | |
| 491 | 12 | V491I, |
| 402 | 12 | H402R, |
| 703 | 13 | |
| 8 | 13 | |
| 765 | 13 | |
| 9 | 13 | A9T, A9V |
| 7 | 13 | |
| 5 | 13 | |
| 706 | 13 | S706C, S706F, |
| 490 | 13 | A490T, A490P, |
| 826 | 13 | T826A, T826I, |
| 702 | 14 | |
| 473 | 14 | T473P, |
| 487 | 14 | G487S, G487R, |
| 493 | 14 | Y493H, Y493C, Y493F, Y493Ins, |
| 699 | 14 | E699D, E699D, |
| 3 | 14 | |
| 496 | 14 | |
| 764 | 14 | |
| 485 | 15 | H485X, |
| 497 | 15 | W497L, W497X, |
| 537 | 15 | R537W, |
| 495 | 15 | K495X, |