SCN5A Variant Y1795H
Summary of observed carriers, functional annotations, and structural context for SCN5A Y1795H. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
23%
2/15 effective observations
Estimated BrS1 penetrance
24%
3/15 effective observations
Total carriers
5
2 BrS1 · 0 LQT3 · 3 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 (%) |
|---|---|---|---|---|---|
| -4.62 | 0.999 | -2.37 | 0.991 | 11 | 64 |
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 |
|---|---|---|---|---|---|---|---|
| 11410597 | 2001 | 5 | 0 | 2 | 0 | ||
| 11076825 | 2000 | 1 | 0 | 0 | 0 | ||
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| 16980337 | 2007 | 5 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 3 | 0 | 2 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 12796143 | 2003 | HEK | ||||
| 11410597 | 2001 | HEK | 66 | 1.1 | -10.5 | 68 |
| 11076825 | 2000 | |||||
| 11901046 | 2002 | |||||
| 12814325 | 2003 | |||||
| 16980337 | 2007 | |||||
| 16798729 | 2006 | HEK | 5 | -11.7 | 343 | |
| 16929919 | 2006 | HEK | 414 |
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 |
|---|---|---|
| 1850 | 7 | C1850S, |
| 1855 | 14 | |
| 1803 | 13 | |
| 1814 | 14 | |
| 1794 | 4 | |
| 1849 | 11 | H1849R, |
| 1856 | 14 | |
| 1806 | 12 | p.Thr1806SerfsX27, |
| 1853 | 10 | I1853V, |
| 1795 | 0 | p.Y1795_E1796insD, Y1795N, Y1795C, Y1795H, |
| 1818 | 13 | |
| 1801 | 11 | |
| 1802 | 10 | |
| 1820 | 13 | A1820T, A1820V, |
| 1504 | 6 | K1504E, |
| 1851 | 9 | M1851I, M1851V, |
| 1501 | 10 | p.L1501_K1505del, L1501V, |
| 1857 | 12 | |
| 1507 | 6 | p.Q1507_P1509del, |
| 1505 | 8 | K1505N, p.K1505_Q1507del, |
| 1858 | 13 | |
| 1509 | 12 | P1509T, |
| 1808 | 12 | |
| 1787 | 13 | S1787N, |
| 1804 | 14 | |
| 1786 | 13 | L1786R, L1786Q, c.5356_5357delCT, |
| 1807 | 10 | c.5420dupA, |
| 1821 | 11 | |
| 1798 | 6 | W1798X, |
| 1854 | 8 | |
| 1825 | 11 | L1825P, |
| 1797 | 8 | I1797V, |
| 1800 | 10 | |
| 1793 | 8 | M1793K, |
| 1789 | 11 | |
| 1848 | 13 | |
| 1817 | 10 | |
| 1796 | 7 | |
| 1799 | 8 | |
| 1788 | 10 | c.5361_5364delTGAG |
| 1638 | 15 | R1638Q, R1638X, |
| 1500 | 11 | p.K1500del, |
| 1791 | 7 | |
| 1852 | 12 | D1852V, |
| 1792 | 7 | D1792N, D1792V, D1792Y, |
| 1508 | 11 | |
| 1502 | 11 | G1502A, G1502S, |
| 1805 | 10 | |
| 1497 | 14 | |
| 1790 | 10 | D1790G, p.D1790del, D1790N, |
| 1809 | 12 | I1809M, |
| 1506 | 6 | P1506S, P1506T, |
| 1503 | 10 | S1503Y, |
| 1822 | 12 | c.5464_5467delTCTG, c.5464-5467delTCTG, |