A1870D Summary

SCN5A A1870D was found in 1 paper (see below) with a total of 0 carriers: 0 had BrS1, 0 had LQT3, and 1 had other disease. A1870D is not present in gnomAD. A1870D has been functionally characterized in 0 papers. Other variants at the same resdue are A1870D .A1870G .A1870P .A1870S .A1870T .A1870V . Given the functional data available, we estimate this variant has "Normal" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Mild_Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

A1870D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2461399520140001irritable bowel syndrome
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A1870D 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
24613995 2014 HEK 83.4 0.6 -1.1 53.8

A1870D 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 0.005 -3.72 possiblydamaging 0.917 1.576 0.03 -3 0.777

A1870D has 19 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
1490 14.7
1494 14.9
1784 14.8 E1784K
1859 12.7
1862 12.3
1863 10.3
1864 13.6
1865 12.3
1866 8.8
1867 5
1868 7.2
1869 4.3
1871 3.8
1872 6.5
1873 8.7
1874 9.2
1875 14.2 p.M1875dup
1877 11.6
1878 14