SCN5A Variant L466F
Summary of observed carriers, functional annotations, and structural context for SCN5A L466F. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/17 effective observations
Estimated BrS1 penetrance
13%
2/17 effective observations
Total carriers
7
1 BrS1 · 0 LQT3 · 6 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.32 | 0.998 | -0.14 | 0.768 | 9 | 6 |
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. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).
Reported carrier data
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 24721456 | 2014 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 7 | 6 | 0 | 1 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
Functional data
Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 24721456 | 2014 |
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 |
|---|---|---|
| 451 | 15 | |
| 452 | 14 | G452D, |
| 453 | 14 | V453M, |
| 454 | 13 | |
| 455 | 13 | |
| 456 | 12 | V456M, |
| 457 | 11 | |
| 458 | 11 | R458C, R458H, p.R458VfsX12, |
| 459 | 10 | S459G, |
| 460 | 9 | |
| 461 | 8 | L461V, |
| 462 | 8 | E462A, E462K, |
| 463 | 7 | M463R, M463T |
| 464 | 5 | |
| 465 | 4 | p.P465LfsX5, |
| 466 | 0 | L466F, L466F, |
| 467 | 4 | |
| 468 | 5 | P468L, |
| 469 | 7 | V469I, |
| 470 | 8 | N470K, N470K, |
| 471 | 8 | |
| 472 | 9 | |
| 473 | 10 | E473X, |
| 474 | 11 | R474G, R474K, |
| 475 | 11 | R475S, R475K, R475S, |
| 476 | 12 | |
| 477 | 13 | c.1428_1431delCAAG, |
| 478 | 13 | |
| 479 | 14 | |
| 480 | 14 | K480N, K480N, |
| 481 | 15 | R481W, R481Q, |