G35S Summary

SCN5A G35S was found in 4 papers (see below) with a total of 28 carriers: 1 had BrS1, 1 had LQT3, and 0 had other disease. G35S is present in 26 out of 279916 alleles in gnomAD (minor allele frequency of 0.009289%). G35S has been functionally characterized in 1 paper. Other variants at the same resdue are G35A .G35C .G35D .G35R .G35S .G35V . 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 Non_Hotspot region for Long QT syndrome.

G35S Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2380510620130000
1196058020010100
1875214220080010
2932597620180100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G35S 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
23805106 2013 HEK 116.1 -1.7 -1.8 NA

G35S 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 0.144 0.89 benign 0.001 2.91 0.49 -2 0.212

G35S 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
20 14.7
21 14.2
22 13.7 A22V
23 13.2
24 12.6
25 12 E25K
26 11.4
27 10.7 R27C R27H R27L
28 10.1 M28I M28I M28I M28L M28L
29 9.3 A29V
30 8.5
31 7.6
32 6.6
33 5.4
34 3.8 R34C R34H
36 3.8
37 5.4 T37A
38 6.6
39 7.6
40 8.5
41 9.3
42 10.1
43 10.7 R43Q
44 11.4
45 12
46 12.6
47 13.2
48 13.7 E48K
49 14.2
50 14.7