KCNQ1 Variant L374H
Summary of observed carriers, functional annotations, and structural context for KCNQ1 L374H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT1 penetrance
62%
10/17 effective observations
Total carriers
7
6 LQT1 · 1 unaffected
Functional studies
0
Publications with functional data
Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT1 (%) |
|---|---|---|---|---|
| -6.59 | 1.0 | -1 | 0.973 | 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 |
|---|---|---|---|---|---|
| 31899541 | 2020 | 6 | None | 6 | None |
| 23631430 | 2013 | 1 | None | None | None |
| 19716085 | 2009 | 1 | None | 1 | None |
| Literature, cohort, and gnomAD | – | 7 | 1 | 6 | – |
| Variant features alone | – | 15 | 6 | 4 | – |
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 |
|---|---|---|
| 374 | 0 | L374H, L374F, |
| 373 | 5 | S373P, |
| 375 | 5 | |
| 525 | 5 | A525T, A525V, |
| 371 | 5 | A371T, |
| 377 | 5 | |
| 522 | 6 | Y522S, |
| 372 | 6 | |
| 378 | 6 | A378T, |
| 529 | 6 | |
| 370 | 6 | A370V, |
| 526 | 7 | K526Q, K526E, |
| 376 | 7 | |
| 524 | 9 | V524G, |
| 528 | 9 | |
| 523 | 9 | |
| 369 | 10 | |
| 530 | 10 | |
| 380 | 10 | R380S, R380S, R380G, |
| 521 | 10 | |
| 381 | 10 | C381Y, |
| 527 | 11 | |
| 379 | 11 | W379R, W379R, W379C, W379C, W379G |
| 368 | 11 | |
| 367 | 11 | Q367H, Q367H, |
| 532 | 12 | |
| 533 | 12 | R533W, R533Q, |
| 519 | 13 | R519H, R519C, |
| 518 | 13 | R518Q, R518G, |
| 531 | 13 | |
| 382 | 13 | |
| 520 | 13 | M520R, |
| 383 | 14 | |
| 534 | 15 | |
| 517 | 15 | I517T, |