SCN5A Variant D536H
Summary of observed carriers, functional annotations, and structural context for SCN5A D536H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
39%
2/12 effective observations
Estimated BrS1 penetrance
8%
0/12 effective observations
Total carriers
2
0 BrS1 · 1 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.13 | 0.998 | -1.53 | 0.676 | 2 | 41 |
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 |
|---|---|---|---|---|---|---|---|
| 27471188 | 2016 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 1 | 0 | – | |
| Variant features alone | – | 15 | 14 | 1 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 27471188 | 2016 |
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 |
|---|---|---|
| 521 | 15 | K521E, c.1562delA, |
| 522 | 14 | P522S, |
| 523 | 14 | R523S, R523C, R523H, |
| 524 | 13 | c.1570_1571insG, S524Y, |
| 525 | 13 | S525G, |
| 526 | 12 | R526C, R526H, |
| 527 | 11 | G527R, G527R, |
| 528 | 11 | S528R, S528R, S528R, |
| 529 | 10 | |
| 530 | 9 | F530V, F530S, |
| 531 | 8 | T531A, T531I, |
| 532 | 8 | F532L, F532C, F532L, F532L, |
| 533 | 7 | R533S, R533C, R533H, |
| 534 | 5 | |
| 535 | 4 | R535G, R535X, R535Q, |
| 536 | 0 | D536H, |
| 537 | 4 | |
| 538 | 5 | G538D, |
| 539 | 7 | |
| 540 | 8 | |
| 541 | 8 | |
| 542 | 9 | |
| 543 | 10 | F543L, F543L, F543L, |
| 544 | 11 | |
| 545 | 11 | |
| 546 | 12 | |
| 547 | 13 | |
| 548 | 13 | |
| 549 | 14 | |
| 550 | 14 | |
| 551 | 15 | A551T, A551V |