SCN5A Variant c.5321_5324dupACTT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.5321_5324dupACTT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
31%
1/11 effective observations
Estimated BrS1 penetrance
35%
3/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 2 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 | 36 | 48 |
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 |
|---|---|---|---|---|---|---|---|
| 23955615 | 2013 | 3 | 0 | 1 | 2 | SSS, AVB | |
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 1 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 23955615 | 2013 |
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 | 13 | M414V, |
| 1659 | 14 | |
| 1643 | 15 | I1643L, |
| 404 | 15 | L404V, L404Q, |
| 1778 | 7 | |
| 1480 | 13 | c.4438-1C>T, c.4437+5G>A, |
| 1773 | 5 | |
| 1653 | 6 | |
| 1472 | 15 | p.N1472del, N1472S, |
| 1771 | 6 | I1771T, |
| 1652 | 5 | M1652T, M1652R, |
| 1777 | 6 | V1777L, V1777M, |
| 409 | 13 | L409V, L409P, |
| 1650 | 8 | L1650F, |
| 1492 | 13 | |
| 1656 | 9 | |
| 1477 | 8 | K1477N, |
| 1471 | 14 | |
| 1779 | 9 | T1779M, |
| 1493 | 14 | p.K1493del, K1493R, K1493X |
| 1470 | 11 | |
| 1478 | 13 | K1478E, |
| 1776 | 6 | |
| 1787 | 13 | S1787N, |
| 1767 | 11 | Y1767C, |
| 1660 | 14 | I1660V, I1660S, |
| 1654 | 10 | |
| 1648 | 9 | |
| 1769 | 8 | |
| 1766 | 13 | M1766L, M1766V, M1766T, |
| 1319 | 14 | G1319V, |
| 1649 | 6 | A1649V, |
| 1768 | 11 | I1768V, |
| 1774 | 0 | N1774D, c.5321_5324dupACTT, |
| 1473 | 10 | F1473C, F1473S, |
| 1657 | 10 | |
| 1496 | 12 | |
| 1474 | 10 | |
| 1481 | 13 | G1481V, G1481E, G1481R, |
| 1781 | 10 | E1781G, E1781D, |
| 1772 | 7 | L1772V, |
| 1645 | 11 | T1645M, |
| 1323 | 14 | V1323G, |
| 410 | 10 | A410V, |
| 1780 | 11 | E1780G, |
| 1788 | 13 | c.5361_5364delTGAG, |
| 1770 | 6 | I1770V, |
| 1651 | 10 | |
| 1500 | 14 | p.K1500del, |
| 413 | 13 | A413E, A413T, |
| 1482 | 14 | |
| 408 | 15 | |
| 1322 | 12 | c.3963+2T>C, c.3963+4A>G, |
| 407 | 11 | |
| 1476 | 13 | Q1476X, Q1476R, |
| 1775 | 7 | p.F1775LfsX15, F1775V, |
| 1642 | 15 | G1642E, |
| 1655 | 11 | |
| 1475 | 14 | Q1475L, p.Q1475NfsX6, |
| 1469 | 14 | I1469V, |
| 406 | 12 | N406S, N406K, |
| 411 | 13 | V411M, |
| 1647 | 12 | |
| 1646 | 10 | |
| 1489 | 14 | E1489D, |
| 1782 | 13 | |
| 1658 | 14 |