SCN5A Variant T1645M
Summary of observed carriers, functional annotations, and structural context for SCN5A T1645M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
26%
3/18 effective observations
Estimated BrS1 penetrance
8%
1/18 effective observations
Total carriers
8
0 BrS1 · 2 LQT3 · 6 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 (%) |
|---|---|---|---|---|---|
| -5.59 | 1 | 2.95 | 0.948 | 14 | 27 |
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 |
|---|---|---|---|---|---|---|---|
| 10508990 | 1999 | 1 | 1 | 0 | 0 | ||
| 10973849 | 2000 | 1 | 1 | 0 | 0 | ||
| 29325976 | 2018 | 2 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 6 | 2 | 0 | – | |
| 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.
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 | 15 | |
| 414 | 12 | M414V, |
| 1785 | 12 | |
| 1643 | 6 | I1643L, |
| 1778 | 7 | |
| 249 | 13 | K249X, |
| 1653 | 13 | |
| 1635 | 15 | |
| 1771 | 13 | I1771T, |
| 1652 | 10 | M1652T, M1652R, |
| 1634 | 12 | L1634P, |
| 1824 | 15 | P1824A |
| 1777 | 11 | V1777M, V1777L, V1777L, |
| 250 | 14 | |
| 1650 | 9 | L1650F, |
| 1641 | 6 | |
| 1639 | 10 | G1639A, |
| 1779 | 8 | T1779M, |
| 1776 | 11 | |
| 1787 | 8 | S1787N, |
| 1654 | 15 | |
| 1786 | 12 | c.5356_5357delCT, L1786Q, L1786R, |
| 1648 | 6 | |
| 1649 | 7 | A1649V, |
| 1774 | 11 | N1774D, c.5321_5324dupACTT, |
| 1644 | 5 | R1644C, R1644H, R1644L, |
| 1640 | 8 | |
| 256 | 12 | |
| 1793 | 13 | M1793K, |
| 1781 | 10 | E1781G, E1781D, E1781D, |
| 1789 | 8 | |
| 255 | 14 | |
| 1772 | 15 | L1772V, |
| 1645 | 0 | T1645M, |
| 251 | 14 | |
| 410 | 13 | A410V, |
| 1780 | 12 | E1780G, |
| 1788 | 9 | c.5361_5364delTGAG, |
| 1638 | 11 | R1638X, R1638Q, |
| 1651 | 10 | |
| 1500 | 14 | p.K1500del, |
| 1633 | 15 | |
| 1791 | 13 | |
| 1637 | 9 | |
| 253 | 12 | |
| 1792 | 12 | D1792N, D1792Y, D1792V, |
| 1636 | 14 | |
| 407 | 12 | |
| 1783 | 12 | |
| 1775 | 8 | F1775V, p.F1775LfsX15, |
| 1642 | 5 | G1642E, |
| 1790 | 10 | D1790N, D1790G, p.D1790del, |
| 252 | 11 | |
| 411 | 12 | V411M, |
| 1647 | 6 | |
| 1822 | 15 | c.5464_5467delTCTG, c.5464-5467delTCTG, |
| 1646 | 5 | |
| 1782 | 8 |