SCN5A Variant S1553R
Summary of observed carriers, functional annotations, and structural context for SCN5A S1553R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/11 effective observations
Estimated BrS1 penetrance
41%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.23 | 0.074 | -2.36 | 0.752 | 50 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 21321465 | 2011 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 21321465 | 2011 |
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 |
|---|---|---|
| 1560 | 10 | L1560F, L1560F, |
| 357 | 15 | |
| 273 | 13 | |
| 1551 | 7 | D1551N, D1551Y, |
| 1559 | 10 | I1559V, |
| 1544 | 14 | T1544P, |
| 1553 | 0 | S1553R, S1553R, S1553R, |
| 1547 | 11 | V1547L, V1547L, |
| 1563 | 14 | |
| 1554 | 4 | |
| 1552 | 4 | Q1552R, Q1552L, |
| 1549 | 9 | |
| 1556 | 5 | |
| 356 | 14 | D356N, |
| 1558 | 8 | |
| 1548 | 10 | G1548K, E1548K, |
| 1550 | 10 | |
| 1561 | 12 | |
| 1557 | 6 | I1557V, |
| 1555 | 5 | E1555K, |
| 1562 | 13 |