KCNH2 Variant R734H
Summary of observed carriers, functional annotations, and structural context for KCNH2 R734H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
9%
1/13 effective observations
Total carriers
3
1 LQT2 · 2 unaffected
Functional studies
0
Publications with functional data
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 (%) |
|---|---|---|---|---|
| -4.498 | 1.0 | 0 | 0.885 | 22 |
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 |
|---|---|---|---|---|---|
| Italy Cohort | 2020 | 3 | 2 | 1 | |
| Literature, cohort, and gnomAD | – | 3 | 2 | 1 | – |
| 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 |
|---|---|---|
| 734 | 0 | R734C, R734H, |
| 731 | 5 | H731R, |
| 735 | 5 | S735L, |
| 738 | 6 | Q738X, |
| 733 | 7 | |
| 732 | 7 | |
| 730 | 7 | |
| 736 | 8 | |
| 737 | 8 | L737P, |
| 739 | 8 | H739fsX, |
| 690 | 10 | |
| 688 | 10 | |
| 687 | 10 | |
| 729 | 10 | |
| 689 | 10 | |
| 783 | 10 | S783P, |
| 728 | 11 | |
| 727 | 11 | |
| 831 | 11 | |
| 784 | 11 | R784G, R784W, R784Q, |
| 740 | 12 | C740G, C740W, |
| 755 | 12 | |
| 693 | 12 | L693X, |
| 829 | 12 | D829A, D829E, D829E |
| 751 | 12 | L751V, |
| 760 | 13 | |
| 726 | 13 | |
| 743 | 13 | |
| 758 | 13 | |
| 802 | 13 | |
| 692 | 13 | |
| 686 | 13 | |
| 781 | 14 | |
| 744 | 14 | R744G, R744fsX, R744X, R744Q, R744P, |
| 691 | 14 | |
| 752 | 14 | R752W, R752Q, R752P, |
| 801 | 14 | K801T, |
| 684 | 14 | |
| 830 | 14 | |
| 782 | 14 | I782fsX, I782N, |
| 754 | 14 | |
| 683 | 14 |