E1208K Summary

SCN5A E1208K was found in 2 papers (see below) with a total of 4 carriers: 0 had BrS1, 1 had LQT3, and 0 had other disease. E1208K is present in 3 out of 247424 alleles in gnomAD (minor allele frequency of 0.001212%). E1208K has been functionally characterized in 1 paper. Other variants at the same resdue are E1208A .E1208D .E1208D .E1208G .E1208K .E1208Q .E1208V . 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 Non_Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

E1208K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2590454120150000
2756675520160010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1208K 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
25904541 2015 HEK 82 -4 -8 71

E1208K 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 -3.91 probablydamaging 0.974 0.1779 -0.87 -4 0.867

E1208K has 32 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
1206 7.6
1207 4.1
1209 5.1
1210 8.5 F1210S
1211 6.4
1212 7.3 p.I1212del
1213 11.5
1214 11.1
1215 11.6 I1215V
1216 13.4
1249 13.9
1250 14.3
1252 13.6
1253 10.3
1254 13.9
1256 11.7
1257 9.9
1260 12.6
1261 12
1266 14.4
1271 14
1272 13.2
1275 13.3 D1275N
1309 11.9 R1309H
1310 13.5
1312 10.5
1313 10
1314 14.3
1315 13.2
1316 7.9 R1316Q
1317 14 F1317C
1321 14.7