A178G Summary

SCN5A A178G was found in 2 papers (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. A178G is not present in gnomAD. A178G has been functionally characterized in 1 paper. Other variants at the same resdue are A178D .A178G .A178P .A178S .A178T .A178V . 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 Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

A178G Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A178G 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
32533946 2020 HEK 109.6 9.2 NA

A178G 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 -3.85 probablydamaging 0.997 0.2118 1.11 -2 0.946

A178G has 44 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
112 10.6
113 10.8
114 7.5
115 10
116 9.5
117 12.8
118 10.7
119 11.8 P119L P119S
120 10.1
121 5.1 R121Q R121W
122 9.4
123 8.7 A123V
124 6
125 4.8 V125L V125L
126 9.6
127 9.2
128 6.7
129 9
130 13.4
133 12
134 13.1
169 14.6
170 11.9
171 11.1
172 10.1
173 8.8
174 6.1
175 6.7
176 6.2
177 4.9
179 3.5 R179Q
180 6.3
181 10.9
182 12.8
183 12.6
184 8.4
185 11.1 A185T A185V
187 11.8 T187S T187S
188 9.3
189 15
191 14.7
194 12.4
197 14.2
198 12.8