D1790G Summary

SCN5A D1790G was found in 22 papers (see below) with a total of 45 carriers: 1 had BrS1, 38 had LQT3, and 0 had other disease. D1790G is not present in gnomAD. D1790G has been functionally characterized in 6 papers. Other variants at the same resdue are D1790A .D1790E .D1790E .D1790G .D1790H .D1790N .D1790V .D1790Y .p.D1790del . Given the functional data available, we estimate this variant has "GOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Non_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

D1790G Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2808762220170000
968675319980000
1115051420000000
10627139199830230
1075805320000000
1097384920000010
1281432520030000
1641494420050010
1914092720090010
20102920201000350
2236081720120020
2630462020151100
26669661201620120
2901792720170000
1240181220030000
27566755201600300
28339995201700850
1095296320000000
2537005020140000
2773349520160080
1092007320000000
3005997320180070
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D1790G Reported Functional Data

Peak current and late current are relative % to wildtype. V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype.

PMID Year Cell type Peak current V0.5 act V0.5 inact Rec from inact Late current
28087622 2017 HEK 81 5.12 -14.8 120.6
9686753 1998 HEK 82.8 0 -16.3 NA
11150514 2000 HEK 100 5.36 -14.64 2000
10952963 2000 HEK NA -15.6 NA
25370050 2014 HEK NA 3.9 -13.5 NA
27733495 2016 tsA201 NA NA
10920073 2000 HEK 0 7 -15 NA

D1790G Predictions

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 is considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. PAM scores reflect the chemistry difference between WT and variant amino acid (more negative being greater difference between the two). BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected.

SIFT Sift Score PROVEAN Score Polyphen2 Polyphen2 Score eaRate blastPssm pamScore REVEL
Damaging 0 -6.47 probablydamaging 1 0.1729 -4.39 -3 0.992

D1790G has 65 neighbors within 15 ångströms that have been found in individuals.

A residue within a folded protein on average has nearest neighbors that fall roughly into two shells: a "nearest" neighbor around 5-6 angstroms and a second shell around 11 angstroms.

ResidueNumber Distance(Å) Variants
1493 14 K1493R p.K1493del
1496 13.3
1497 10.8
1498 14.2 M1498R M1498T
1500 9.4
1501 11.4 L1501V
1502 14.8 G1502A G1502S
1503 13.6
1504 11.2
1637 14
1638 10.6 R1638Q
1639 12.5 G1639A
1640 13.6
1641 8.7
1642 13.2
1644 10.2 R1644C R1644H
1645 10.1 T1645M
1646 15
1647 14.9
1648 11
1649 14.4
1652 14.8
1777 14.7 V1777M
1778 11.8
1779 13.7 T1779M
1780 14.9
1781 10.1 E1781G
1782 9.5
1783 12.2
1784 12.9 E1784K
1785 9.1
1786 5.1 L1786Q
1787 4.2 S1787N
1788 6.7
1789 4.4
1791 5
1792 6.6 D1792N
1793 6.3 M1793K
1794 8.1
1795 10.4 p.Y1795_E1796insD Y1795C Y1795H
1796 10.4
1797 11
1798 14.1
1817 13.2
1818 13.5
1820 12.4 A1820T
1821 9.2
1822 6.9
1823 9.2 E1823K
1824 7.3
1825 6.8 L1825P
1826 10.9 R1826C R1826H
1827 13.9
1850 14.9
1853 13.9
1854 10.8
1855 14.9
1856 14.2
1857 11.7
1858 9.6
1860 14
1861 9.9
1862 12.6
1864 14.4
1865 14.2