A1113V Summary

SCN5A A1113V was found in 2 papers (see below) with a total of 7 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. A1113V is present in 6 out of 240468 alleles in gnomAD (minor allele frequency of 0.002495%). A1113V has been functionally characterized in 1 paper. Other variants at the same resdue are A1113D .A1113G .A1113P .A1113S .A1113T .A1113V . 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.

A1113V Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2457316420140000
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A1113V 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 100 -0.78 NA

A1113V 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 0.323 0.45 benign 0.136 1 -0.66 -2 0.521

A1113V 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
1098 14.7 V1098L V1098L V1098M
1099 14.2
1100 13.7 A1100V
1101 13.2
1102 12.6 A1102T
1103 12 S1103F S1103Y
1104 11.4
1105 10.7
1106 10.1 A1106T
1107 9.3 E1107K
1108 8.5
1109 7.6 S1109G
1110 6.6
1111 5.4
1112 3.8
1114 3.8 D1114E D1114E D1114N
1115 5.4
1116 6.6 R1116Q R1116W
1117 7.6
1118 8.5
1119 9.3
1120 10.1
1121 10.7 A1121V
1122 11.4
1123 12
1124 12.6
1125 13.2 A1125G A1125V
1126 13.7
1127 14.2
1128 14.7