SCN5A Variant S524Y
Summary of observed carriers, functional annotations, and structural context for SCN5A S524Y. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/1179 effective observations
Estimated BrS1 penetrance
0%
2/1179 effective observations
Total carriers
1169
0 BrS1 · 0 LQT3 · 1169 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.55 | 0.959 | -1.03 | None | 29 | 2 |
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 |
|---|---|---|---|---|---|---|---|
| 16453024 | 2006 | 3 | 0 | 0 | 2 | SIDS | |
| 23571586 | 2013 | 1 | 0 | 0 | 1 | stillbirth, SUDS | |
| 20129283 | 2010 | 18 | 0 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1169 | 1169 | 0 | 0 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 17331104 | 2007 | HEK | 113 | -5 | 1.6 | |
| 15851227 | 2004 | |||||
| 15898185 | 2004 | |||||
| 15992732 | 2005 | HEK | 84 | -1 | -2 | |
| 16453024 | 2006 | |||||
| 23571586 | 2013 | |||||
| 15992733 | 2005 | |||||
| 20129283 | 2010 |
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 |
|---|---|---|
| 509 | 15 | |
| 510 | 14 | |
| 511 | 14 | |
| 512 | 13 | T512I, |
| 513 | 13 | R513C, c.1537delC, R513H, R513P, |
| 514 | 12 | G514C, |
| 515 | 11 | |
| 516 | 11 | |
| 517 | 10 | R517S, |
| 518 | 9 | |
| 519 | 8 | S519F, |
| 520 | 8 | M520R, M520V, |
| 521 | 7 | K521E, c.1562delA, |
| 522 | 5 | P522S |
| 523 | 4 | R523C, R523H, R523S, |
| 524 | 0 | c.1570_1571insG, S524Y, |
| 525 | 4 | S525G, |
| 526 | 5 | R526H, R526C, |
| 527 | 7 | G527R, |
| 528 | 8 | S528R, |
| 529 | 8 | |
| 530 | 9 | F530V, F530S, |
| 531 | 10 | T531I, T531A, |
| 532 | 11 | F532L, F532C, |
| 533 | 11 | R533C, R533H, R533S, |
| 534 | 12 | |
| 535 | 13 | R535Q, R535X, R535G, |
| 536 | 13 | D536H, |
| 537 | 14 | |
| 538 | 14 | G538D, |
| 539 | 15 |