KCNQ1 Variant R259L
Summary of observed carriers, functional annotations, and structural context for KCNQ1 R259L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT1 penetrance
58%
9/16 effective observations
Total carriers
6
6 LQT1 · 0 unaffected
Functional studies
0
Publications with functional data
Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT1 (%) |
|---|---|---|---|---|
| -6.8 | 0.982 | -1 | 0.948 | 45 |
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 |
|---|---|---|---|---|---|
| 33664273 | 2021 | 1 | 0 | 1 | None |
| 32893267 | 2020 | 2 | None | 2 | None |
| 23631430 | 2013 | 1 | None | None | None |
| 22949429 | 2012 | 1 | None | 1 | None |
| 19841300 | 2009 | 1 | None | 1 | None |
| 19716085 | 2009 | 1 | None | 1 | None |
| 19490272 | 2009 | 5 | None | 5 | None |
| 18752142 | 2008 | 12 | None | 3 | RWS |
| Literature, cohort, and gnomAD | – | 6 | 0 | 6 | – |
| Variant features alone | – | 15 | 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 259 | 0 | R259C, R259H, R259L, R259G, |
| 256 | 5 | |
| 263 | 6 | |
| 266 | 11 | L266P, |
| 359 | 12 | Q359del, |
| 351 | 13 | F351L, F351L, F351L, F351S, |
| 250 | 13 | L250H, L250P, |
| 355 | 13 | |
| 267 | 14 | Y267C |
| 251 | 14 | L251P, L251Q, |
| 261 | 14 | E261K, E261D, E261D, E261G, E261Q, |
| 354 | 14 | |
| 254 | 14 | V254M, V254L, V254L, |
| 358 | 14 | K358T, |
| 247 | 15 | T247I, |
| 350 | 15 | G350V, G350R, G350R, G350W, |
| 260 | 15 |