D1819N Summary

SCN5A D1819N was found in 5 papers (see below) with a total of 72 carriers: 0 had BrS1, 1 had LQT3, and 1 had other disease. D1819N is present in 71 out of 281162 alleles in gnomAD (minor allele frequency of 0.025252%). D1819N has been functionally characterized in 2 papers. Other variants at the same resdue are D1819A .D1819E .D1819E .D1819G .D1819H .D1819N .D1819V .D1819Y . Given the functional data available, we estimate this variant has "Mild_LOF" 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 Non_Hotspot region for Long QT syndrome.

D1819N Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2268511320120001AF
2590454120150000
2414488320140001AF
1692272420060010
2932597620180100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D1819N 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
22685113 2012 HEK 71.4 0.13 0.2 NA
25904541 2015 HEK 76 -2 -1 88

D1819N 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 0.01 -2.9 possiblydamaging 0.919 0.5226 -0.1 2 0.729

D1819N has 36 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
1793 12.6 M1793K
1794 12.3
1796 15
1797 10.1
1798 13.7
1800 12.5
1801 10.6
1809 13.9
1811 14.3
1812 13 S1812L
1813 10.6
1814 9.5
1815 6.4
1816 5.9
1817 7.4
1818 4.6
1820 4.4 A1820T
1821 6.4
1822 8.9
1823 10.3 E1823K
1824 12.1
1825 10.2 L1825P
1826 6.1 R1826C R1826H
1827 6.3
1828 5.1 A1828T
1829 5.1
1830 9
1831 7.5
1832 12 Q1832E
1833 14.3
1834 12.1
1835 11
1838 15
1853 13.6
1857 11.4
1860 13