E48K Summary

SCN5A E48K was found in 3 papers (see below) with a total of 19 carriers: 0 had BrS1, 2 had LQT3, and 0 had other disease. E48K is present in 17 out of 278150 alleles in gnomAD (minor allele frequency of 0.006112%). E48K has been functionally characterized in 1 paper. Other variants at the same resdue are E48A .E48D .E48D .E48G .E48K .E48Q .E48V . Given the functional data available, we estimate this variant has "Mild_LOF" 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.

E48K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2590454120150000
2674645720160010
1971608520090010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E48K 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 63 4 -3 NA

E48K 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 0.166 -1.95 probablydamaging 0.997 2.175 0.63 -4 0.723

E48K 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
33 14.7
34 14.2 R34C R34H
35 13.7 G35S
36 13.2
37 12.6 T37A
38 12
39 11.4
40 10.7
41 10.1
42 9.3
43 8.5 R43Q
44 7.6
45 6.6
46 5.4
47 3.8
49 3.8
50 5.4
51 6.6 A51V
52 7.6 P52S
53 8.5 R53Q
54 9.3
55 10.1
56 10.7
57 11.4
58 12
59 12.6
60 13.2 A60P
61 13.7
62 14.2
63 14.7 K63N K63N