E1053K Summary

SCN5A E1053K was found in 12 papers (see below) with a total of 40 carriers: 5 had BrS1, 2 had LQT3, and 1 had other disease. E1053K is present in 28 out of 280210 alleles in gnomAD (minor allele frequency of 0.009993%). E1053K has been functionally characterized in 2 papers. Other variants at the same resdue are E1053A .E1053D .E1053D .E1053G .E1053K .E1053Q .E1053V . 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 Non_Hotspot region for Long QT syndrome.

E1053K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2457316420140000
1557953420040000
1107682520000100
1190104620020100
1902662320090010
2332162020130100
2674645720161000
2839111420174001SUDS
1971608520090010
2012928320100300
2957918920180001Afib
3005997320180010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1053K 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
24573164 2014 HEK 75 3.71 NA
15579534 2004 HEK 100 -8.3 -4.7 NA

E1053K 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 -3.73 probablydamaging 0.999 1.534 -0.22 -4 0.872

E1053K 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
1038 14.7
1039 14.2
1040 13.7 G1040R G1040R
1041 13.2 D1041N
1042 12.6
1043 12
1044 11.4
1045 10.7 V1045M
1046 10.1
1047 9.3
1048 8.5
1049 7.6
1050 6.6 A1050T
1051 5.4
1052 3.8
1054 3.8
1055 5.4
1056 6.6
1057 7.6
1058 8.5
1059 9.3
1060 10.1
1061 10.7 E1061D E1061D
1062 11.4
1063 12
1064 12.6 p.E1064del
1065 13.2
1066 13.7 S1066G
1067 14.2
1068 14.7 G1068D