SCN5A Variant p.F1775LfsX15
Summary of observed carriers, functional annotations, and structural context for SCN5A p.F1775LfsX15. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
44%
3/13 effective observations
Estimated BrS1 penetrance
22%
2/13 effective observations
Total carriers
3
1 BrS1 · 2 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 20 | 40 |
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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 0 | 2 | 1 | – | |
| Variant features alone | – | 15 | 13 | 1 | 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) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
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 |
|---|---|---|
| 403 | 12 | |
| 414 | 7 | M414V, |
| 939 | 14 | L939F, |
| 1785 | 15 | |
| 1643 | 11 | I1643L, |
| 404 | 12 | L404V, L404Q, |
| 1778 | 6 | |
| 1773 | 8 | |
| 249 | 11 | K249X, |
| 1653 | 10 | |
| 254 | 15 | |
| 1771 | 7 | I1771T, |
| 1652 | 9 | M1652T, M1652R, |
| 1777 | 7 | V1777M, V1777L, V1777L, |
| 418 | 13 | E418K, |
| 250 | 12 | |
| 409 | 9 | L409V, L409P, |
| 1650 | 8 | L1650F, |
| 1656 | 15 | |
| 1641 | 14 | |
| 417 | 13 | |
| 1477 | 14 | K1477N, K1477N, |
| 246 | 13 | |
| 1779 | 6 | T1779M, |
| 412 | 10 | V412D, |
| 935 | 15 | L935P, |
| 1493 | 14 | p.K1493del, K1493X, K1493R, |
| 1470 | 13 | |
| 245 | 15 | Q245K, |
| 1776 | 5 | |
| 1787 | 13 | S1787N, |
| 1767 | 14 | Y1767C, |
| 1654 | 14 | |
| 1648 | 10 | |
| 1769 | 11 | |
| 415 | 11 | A415T, |
| 1649 | 6 | A1649V, |
| 1768 | 12 | I1768V, |
| 1774 | 7 | N1774D, c.5321_5324dupACTT, |
| 1473 | 14 | F1473S, F1473C, |
| 1644 | 13 | R1644C, R1644H, R1644L, |
| 256 | 14 | |
| 405 | 13 | |
| 1657 | 14 | |
| 1474 | 13 | |
| 1781 | 10 | E1781G, E1781D, E1781D, |
| 1772 | 6 | L1772V, |
| 1645 | 8 | T1645M, |
| 251 | 15 | |
| 410 | 5 | A410V, |
| 1780 | 9 | E1780G, |
| 1788 | 14 | c.5361_5364delTGAG |
| 1770 | 11 | I1770V, |
| 1651 | 12 | |
| 416 | 15 | Y416C, |
| 413 | 9 | A413T, A413E, |
| 408 | 10 | |
| 253 | 11 | |
| 407 | 7 | |
| 1783 | 12 | |
| 936 | 14 | |
| 1775 | 0 | F1775V, p.F1775LfsX15, |
| 1642 | 10 | G1642E, |
| 406 | 10 | N406S, N406K, N406K, |
| 252 | 13 | |
| 411 | 7 | V411M, |
| 932 | 14 | |
| 1647 | 10 | |
| 1646 | 6 | |
| 1489 | 15 | E1489D, E1489D, |
| 1782 | 10 |