SCN5A Variant F532C
Summary of observed carriers, functional annotations, and structural context for SCN5A F532C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
20%
3/22 effective observations
Estimated BrS1 penetrance
24%
5/22 effective observations
Total carriers
12
4 BrS1 · 3 LQT3 · 5 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 (%) |
|---|---|---|---|---|---|
| -4.75 | 0.999 | 0.15 | 0.89 | 9 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 18596570 | 2008 | 1 | 0 | 0 | 1 | SIDS | |
| 15996170 | 2005 | 1 | 0 | 0 | 1 | AF, AT, MS | |
| 20541041 | 2010 | 3 | 3 | 0 | 0 | ||
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 29062695 | 2017 | 2 | 0 | 2 | 0 | ||
| 26746457 | 2016 | 1 | 0 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 12 | 5 | 3 | 4 | – | |
| 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.
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 |
|---|---|---|
| 517 | 15 | R517S, R517S, |
| 518 | 14 | |
| 519 | 14 | S519F, |
| 520 | 13 | M520V, M520R, |
| 521 | 13 | K521E, c.1562delA, |
| 522 | 12 | P522S, |
| 523 | 11 | R523S, R523C, R523H, |
| 524 | 11 | c.1570_1571insG, S524Y, |
| 525 | 10 | S525G, |
| 526 | 9 | R526C, R526H, |
| 527 | 8 | G527R, G527R, |
| 528 | 8 | S528R, S528R, S528R, |
| 529 | 7 | |
| 530 | 5 | F530V, F530S, |
| 531 | 4 | T531A, T531I, |
| 532 | 0 | F532L, F532C, F532L, F532L, |
| 533 | 4 | R533S, R533C, R533H, |
| 534 | 5 | |
| 535 | 7 | R535G, R535X, R535Q, |
| 536 | 8 | D536H, |
| 537 | 8 | |
| 538 | 9 | G538D, |
| 539 | 10 | |
| 540 | 11 | |
| 541 | 11 | |
| 542 | 12 | |
| 543 | 13 | F543L, F543L, F543L |
| 544 | 13 | |
| 545 | 14 | |
| 546 | 14 | |
| 547 | 15 |