E1025D Summary

SCN5A E1025D was found in 1 paper (see below) with a total of 0 carriers: 0 had BrS1, 0 had LQT3, and 1 had other disease. E1025D is not present in gnomAD. E1025D has been functionally characterized in 1 paper. Other variants at the same resdue are E1025A .E1025D .E1025D .E1025G .E1025K .E1025Q .E1025V . 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 Non_Hotspot region for Long QT syndrome.

E1025D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2679838720160001SSS
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1025D 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
26798387 2016 HEK 127.6 -10.93 -5.4 NA

E1025D 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
Tolerated 0.662 0.33 possiblydamaging 0.92 3.75 2.28 2 0.501

E1025D has 30 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
1010 14.7
1011 14.2 P1011L P1011S
1012 13.7
1013 13.2
1014 12.6 P1014S
1015 12
1016 11.4 T1016M
1017 10.7
1018 10.1
1019 9.3
1020 8.5
1021 7.6 P1021S
1022 6.6
1023 5.4 R1023C R1023H R1023P
1024 3.8
1026 3.8
1027 5.4 R1027Q
1028 6.6
1029 7.6
1030 8.5
1031 9.3
1032 10.1 E1032K
1033 10.7 Q1033R
1034 11.4
1035 12
1036 12.6
1037 13.2
1038 13.7
1039 14.2
1040 14.7 G1040R G1040R