KCNH2 Variant D609N
Summary of observed carriers, functional annotations, and structural context for KCNH2 D609N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
60%
13/21 effective observations
Total carriers
11
10 LQT2 · 1 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 0%. 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 3 individuals with LQT2 and 7 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT2 (%) |
|---|---|---|---|---|
| -4.342 | 0.786 | 1 | 0.8 | 90 |
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 |
|---|---|---|---|---|---|
| 11854117 | 2002 | 5 | 0 | 5 | |
| France Cohort | 2020 | 5 | 1 | 4 | |
| 10973849 | 2000 | 1 | 0 | 1 | |
| 18808722 | 2008 | 1 | 0 | 1 | |
| Literature, cohort, and gnomAD | – | 11 | 1 | 10 | – |
| Variant features alone | – | 10 | 7 | 3 | – |
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 |
|---|---|---|
| 609 | 0 | D609N, D609G, |
| 610 | 5 | |
| 606 | 5 | S606Del, S606P, S606F, |
| 608 | 5 | |
| 612 | 5 | V612L, V612L, V612A, |
| 635 | 6 | N635I, |
| 613 | 6 | T613A, T613L, T613K, T613M, |
| 607 | 6 | |
| 611 | 7 | Y611D, |
| 605 | 7 | P605L, |
| 638 | 8 | K638E, K638D, K638Del, K638R, |
| 614 | 8 | A614T, A614V, |
| 589 | 8 | L589P, |
| 593 | 9 | I593V, I593K, I593T, I593R, I593X, |
| 634 | 9 | T634P, T634A, T634S, T634S, T634I, |
| 595 | 10 | K595E, K595N, K595N, |
| 615 | 10 | L615V, L615F, |
| 586 | 10 | L586M, |
| 569 | 10 | Y569H, Y569C, Y569X, |
| 431 | 10 | F431L, F431L, F431L, |
| 639 | 10 | I639F, I639N, |
| 616 | 10 | Y616S, |
| 604 | 10 | G604S, G604C, G604D, |
| 636 | 10 | |
| 633 | 10 | N633D, N633S, N633I, |
| 585 | 11 | W585C, W585C, |
| 590 | 11 | G590D, G590V, |
| 592 | 11 | Q592X, |
| 565 | 12 | |
| 594 | 12 | |
| 427 | 12 | Y427H, Y427S, Y427C, |
| 637 | 12 | E637K, E637G, E637X, |
| 632 | 12 | P632A, P632S, |
| 630 | 12 | V630I, V630T, V630A, |
| 568 | 13 | W568C, W568C, |
| 566 | 13 | C566S, C566R, C566G, C566S, C566F, |
| 617 | 13 | F617L, F617V, F617L, F617L, |
| 629 | 13 | N629D, N629T, N629S, N629I, N629K, N629K, |
| 642 | 13 | I642V, I642Del |
| 588 | 13 | N588D, N588K, N588K, |
| 603 | 13 | G603D, |
| 562 | 14 | H562P, H562R, H562Q, H562Q, |
| 573 | 14 | |
| 597 | 14 | Y597H, Y597C, |
| 430 | 14 | |
| 641 | 14 | S641P, S641F, |
| 596 | 14 | P596T, P596S, P596R, P596L, |
| 591 | 14 | D591N, D591H, |
| 583 | 14 | I583V, |
| 572 | 14 | G572S, G572R, G572C, G572D, |
| 618 | 14 | T618S, T618S, |
| 587 | 14 | |
| 584 | 15 | G584S, G584R, G584C, |
| 570 | 15 | |
| 432 | 15 | |
| 575 | 15 | E575K, |
| 619 | 15 |