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

Y1795H has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near Y1795H.
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,