SCN5A Variant R504T
Summary of observed carriers, functional annotations, and structural context for SCN5A R504T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
26%
2/13 effective observations
Estimated BrS1 penetrance
6%
0/13 effective observations
Total carriers
3
0 BrS1 · 1 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -3.89 | 0.789 | -0.35 | 0.444 | 5 | 21 |
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 |
|---|---|---|---|---|---|---|---|
| 27871843 | 2017 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 2 | 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) |
|---|---|---|---|---|---|---|
| 27871843 | 2017 |
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 |
|---|---|---|
| 489 | 15 | |
| 490 | 14 | G490E, G490A, |
| 491 | 14 | E491G, |
| 492 | 13 | |
| 493 | 13 | R493K, |
| 494 | 12 | |
| 495 | 11 | |
| 496 | 11 | K496M, K496N, K496N, |
| 497 | 10 | S497C, |
| 498 | 9 | |
| 499 | 8 | |
| 500 | 8 | E500K, |
| 501 | 7 | D501G, |
| 502 | 5 | |
| 503 | 4 | P503S, |
| 504 | 0 | R504T, |
| 505 | 4 | A505E, |
| 506 | 5 | M506K, |
| 507 | 7 | p.N507_L515dup, |
| 508 | 8 | |
| 509 | 8 | |
| 510 | 9 | |
| 511 | 10 | |
| 512 | 11 | T512I, |
| 513 | 11 | R513C, c.1537delC, R513H, R513P, |
| 514 | 12 | G514C, |
| 515 | 13 | |
| 516 | 13 | |
| 517 | 14 | R517S, R517S, |
| 518 | 14 | |
| 519 | 15 | S519F |