SCN5A Variant S528R
Summary of observed carriers, functional annotations, and structural context for SCN5A S528R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/12 effective observations
Estimated BrS1 penetrance
9%
1/12 effective observations
Total carriers
2
0 BrS1 · 0 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -4.77 | 0.979 | -1.84 | 0.674 | 5 | 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 |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 2 | 2 | 0 | 0 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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 |
|---|---|---|
| 513 | 15 | R513C, R513P, c.1537delC, R513H, |
| 514 | 14 | G514C, |
| 515 | 14 | |
| 516 | 13 | |
| 517 | 13 | R517S, R517S, |
| 518 | 12 | |
| 519 | 11 | S519F, |
| 520 | 11 | M520V, M520R, |
| 521 | 10 | c.1562delA, K521E, |
| 522 | 9 | P522S, |
| 523 | 8 | R523H, R523C, R523S, |
| 524 | 8 | c.1570_1571insG, S524Y, |
| 525 | 7 | S525G, |
| 526 | 5 | R526H, R526C, |
| 527 | 4 | G527R, G527R, |
| 528 | 0 | S528R, S528R, S528R, |
| 529 | 4 | |
| 530 | 5 | F530S, F530V, |
| 531 | 7 | T531I, T531A, |
| 532 | 8 | F532C, F532L, F532L, F532L, |
| 533 | 8 | R533H, R533C, R533S, |
| 534 | 9 | |
| 535 | 10 | R535X, R535G, R535Q, |
| 536 | 11 | D536H, |
| 537 | 11 | |
| 538 | 12 | G538D, |
| 539 | 13 | |
| 540 | 13 | |
| 541 | 14 | |
| 542 | 14 | |
| 543 | 15 | F543L, F543L, F543L, |