SCN5A Variant F1594S
Summary of observed carriers, functional annotations, and structural context for SCN5A F1594S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
58%
3/11 effective observations
Estimated BrS1 penetrance
10%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.21 | 0.997 | -5.13 | 0.975 | 1 | 67 |
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 |
|---|---|---|---|---|---|---|---|
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 2 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 19716085 | 2009 |
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 |
|---|---|---|
| 1627 | 11 | |
| 1586 | 10 | |
| 1624 | 10 | V1624I, |
| 1538 | 13 | |
| 1635 | 13 | |
| 1587 | 10 | F1587V, |
| 1634 | 14 | L1634P |
| 1602 | 14 | |
| 1534 | 15 | |
| 1601 | 12 | L1601H, |
| 1575 | 12 | C1575S, C1575S, |
| 1600 | 12 | |
| 1571 | 13 | F1571C, |
| 1599 | 11 | |
| 1630 | 11 | I1630V, I1630R, |
| 1626 | 11 | R1626C, R1626H, R1626P, R1626L, |
| 1625 | 7 | |
| 1596 | 8 | F1596I, F1596C, |
| 1628 | 7 | |
| 1589 | 8 | |
| 1632 | 9 | R1632C, R1632H, R1632L, |
| 1597 | 6 | V1597M, |
| 1535 | 14 | |
| 1594 | 0 | F1594S, |
| 1633 | 14 | |
| 1588 | 11 | T1588I, |
| 1591 | 6 | W1591X, |
| 1593 | 5 | I1593M, |
| 1595 | 6 | |
| 1629 | 7 | R1629G, R1629X, R1629Q, |
| 1574 | 13 | c.4719C>T, E1574K, |
| 1541 | 15 | |
| 1592 | 7 | |
| 1578 | 13 | c.4732_4733dupAA, |
| 1631 | 10 | G1631D, |
| 1590 | 5 | |
| 1622 | 12 | |
| 1621 | 12 | |
| 1579 | 14 | L1579fsX53, |
| 1598 | 8 | V1598A, |
| 1623 | 15 | c.4867delC, R1623X, R1623Q, R1623L, |