A124D Summary

SCN5A A124D was found in 1 paper (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. A124D is not present in gnomAD. A124D has been functionally characterized in 0 papers. Other variants at the same resdue are A124D .A124G .A124P .A124S .A124T .A124V . Given the functional data available, we estimate this variant has "Partial_LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

A124D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2252981120120100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A124D 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
22529811 2012 tsA201 23.5 3.6 3.2 NA

A124D 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 -5.23 probablydamaging 0.986 0.7846 -6.34 -3 0.936

A124D has 37 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
114 11.2
115 12.3
116 11.7
117 13.8
118 10.5
119 9.1 P119L P119S
120 6.7
121 6.2 R121Q R121W
122 8.1
123 3.6 A123V
125 4 V125L V125L
126 6
127 4.7
128 6.4
129 8.4
130 10.4
131 13.6
132 13.6
133 9.6
134 12.4
136 14.9 L136P
137 14.4 I137V
169 14.3
170 9.5
171 11.1
172 11.4
173 8.9
174 5.6
175 9.3
176 10
177 6.4
178 6
179 9.3 R179Q
180 11.4
181 14.8
184 14.2
188 14.4