E1295K Summary

SCN5A E1295K was found in 1 paper (see below) with a total of 2 carriers: 0 had BrS1, 1 had LQT3, and 0 had other disease. E1295K is present in 1 out of 248554 alleles in gnomAD (minor allele frequency of 0.000402%). E1295K has been functionally characterized in 1 paper. Other variants at the same resdue are E1295A .E1295D .E1295D .E1295G .E1295K .E1295Q .E1295V . 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.

E1295K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1130449820010010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1295K 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
11304498 2001 HEK 102 2.9 5.2 NA

E1295K 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 0.001 -3.11 probablydamaging 0.99 1.332 -0.88 -4 0.845

E1295K has 16 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
1284 13.6
1285 13.7
1287 11.8
1288 9.1
1289 11.4
1290 9.4
1291 5
1292 5.5
1293 7.7 F1293S
1294 4.8 A1294G
1296 5.2
1297 5.3
1298 8.5 P1298L
1299 10.9
1300 14.2
1734 13.8