A185T Summary

SCN5A A185T was found in 2 papers (see below) with a total of 123 carriers: 0 had BrS1, 3 had LQT3, and 0 had other disease. A185T is present in 116 out of 278414 alleles in gnomAD (minor allele frequency of 0.041665%). A185T has been functionally characterized in 1 paper. Other variants at the same resdue are A185E .A185G .A185P .A185S .A185T .A185V . 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 Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

A185T Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2590454120150000
1517642520044030
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A185T 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 56 3 7 243

A185T 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 0.103 -0.6 possiblydamaging 0.873 2.454 -0.95 -1 0.533

A185T has 33 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 12.5
113 9.8
114 10.5
121 14.2 R121Q R121W
171 14.3
172 10.9
173 12.1
174 13
175 10.3
176 6.9
177 11.1
178 11.1
179 9.7 R179Q
180 6.3
181 7.4
182 5.5
183 6.4
184 5.5
186 5.4
187 5.2 T187S T187S
188 4.8
189 5.7
190 9.3 R190G R190L R190Q R190W
191 10.2
192 12.6
194 9.5
195 11.2
196 13.9
197 12.3
198 8.6
199 12.5
201 14.3
202 13.3