KCNQ1 Variant R583H
Summary of observed carriers, functional annotations, and structural context for KCNQ1 R583H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT1 penetrance
56%
13/24 effective observations
Total carriers
14
8 LQT1 · 6 unaffected
Functional studies
0
Publications with functional data
Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT1 (%) |
|---|---|---|---|---|
| -1.79 | 0.269 | -1 | 0.776 | 56 |
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 | LQT1 | Other Disease |
|---|---|---|---|---|---|
| 32893267 | 2020 | 4 | None | 4 | None |
| 28749435 | 2017 | 3 | 1 | 2 | Digenic mutation burden |
| 26496715 | 2016 | 2 | None | 2 | None |
| 26423924 | 2016 | 1 | None | None | 1 SUDEP |
| 24606995 | 2014 | 1 | None | 1 | None |
| 24363352 | 2014 | 1 | None | None | None |
| 15851171 | 2004 | 2 | 1 | 1 | None |
| Literature, cohort, and gnomAD | – | 14 | 6 | 8 | – |
| Variant features alone | – | 15 | 5 | 5 | – |
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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 583 | 0 | R583H, R583C, R583G, |
| 582 | 4 | |
| 584 | 4 | G584S, |
| 581 | 5 | |
| 585 | 5 | S585N, |
| 580 | 7 | S580G, S580N, |
| 586 | 7 | N586D, |
| 579 | 8 | |
| 587 | 8 | T587M, T587R, |
| 578 | 8 | E578K, E578V, |
| 588 | 8 | I588F, |
| 577 | 9 | |
| 589 | 9 | G589D, G589S, |
| 576 | 10 | V576I, |
| 590 | 10 | A590T, |
| 575 | 11 | |
| 591 | 11 | R591H, R591C, R591L, |
| 574 | 11 | I574V, |
| 592 | 11 | |
| 573 | 12 | F573L, F573L, F573L, |
| 593 | 12 | N593S, |
| 572 | 13 | |
| 594 | 13 | R594Q, R594P, |
| 571 | 13 | S571L, S571P, |
| 595 | 13 | V595L, V595L |
| 570 | 14 | P570L, |
| 596 | 14 | E596del, E596K, |
| 569 | 14 | K569E, |
| 597 | 14 | |
| 568 | 15 | G568R, G568R, G568E, |
| 598 | 15 | K598R, |