SCN5A Variant S1672Y
Summary of observed carriers, functional annotations, and structural context for SCN5A S1672Y. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/13 effective observations
Estimated BrS1 penetrance
64%
8/13 effective observations
Total carriers
3
3 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.16 | 0.996 | -5.06 | 0.951 | 75 | 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 |
|---|---|---|---|---|---|---|---|
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 17404158 | 2007 | 3 | 0 | 3 | 0 | ||
| 26921764 | 2016 | 3 | 0 | 3 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 0 | 0 | 3 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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 |
|---|---|---|
| 1702 | 11 | |
| 387 | 15 | |
| 1218 | 15 | S1218T, S1218I, |
| 1304 | 10 | T1304M, |
| 1698 | 9 | A1698T, |
| 1220 | 12 | G1220E, |
| 1673 | 4 | |
| 1675 | 6 | |
| 1754 | 13 | |
| 1707 | 11 | |
| 1694 | 7 | |
| 1704 | 7 | L1704H, |
| 1226 | 9 | |
| 1706 | 13 | Q1706H, Q1706H, |
| 1747 | 14 | V1747M, |
| 1695 | 11 | Q1695X, |
| 1716 | 14 | p.L1716SfsX71, |
| 1669 | 6 | |
| 1671 | 7 | |
| 1221 | 13 | A1221V, |
| 1668 | 7 | M1668T, |
| 1676 | 5 | M1676T, M1676I, M1676I, M1676I, |
| 1692 | 14 | |
| 1219 | 11 | S1219N, |
| 1672 | 0 | S1672Y, |
| 1693 | 11 | |
| 1699 | 10 | |
| 1310 | 14 | |
| 1306 | 15 | R1306S, R1306H, |
| 1665 | 10 | |
| 1305 | 13 | |
| 1680 | 12 | A1680T, A1680P, |
| 1703 | 9 | |
| 1663 | 14 | |
| 1759 | 14 | S1759C |
| 1701 | 7 | M1701I, M1701I, M1701I, |
| 1307 | 10 | |
| 1758 | 14 | I1758V, p.I1758del, |
| 1228 | 14 | Y1228H, Y1228C, Y1228F, |
| 1678 | 10 | N1678S, |
| 1223 | 8 | c.3667delG, |
| 1755 | 10 | |
| 1697 | 8 | |
| 1222 | 10 | p.L1222LfsX7, L1222R, |
| 1227 | 12 | |
| 1674 | 7 | F1674V, |
| 390 | 14 | |
| 1748 | 14 | p.G1748del, G1748D, |
| 1708 | 12 | T1708I, |
| 1301 | 12 | |
| 1696 | 9 | |
| 1705 | 11 | |
| 1700 | 5 | |
| 1751 | 9 | |
| 1311 | 15 | L1311P, |
| 1677 | 9 | |
| 1682 | 14 | |
| 1308 | 12 | L1308F, |
| 1752 | 12 | |
| 1224 | 11 | |
| 1670 | 6 | |
| 1225 | 11 | E1225K, G1225K, |
| 1720 | 14 | c.5157delC, |
| 1679 | 9 | |
| 1667 | 9 | V1667I, |
| 1664 | 13 | |
| 1303 | 14 | R1303W, R1303Q, |
| 1666 | 10 |