A166T Summary

SCN5A A166T was found in 1 paper (see below) with a total of 70 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. A166T is present in 70 out of 280216 alleles in gnomAD (minor allele frequency of 0.024981%). A166T has been functionally characterized in 1 paper. Other variants at the same resdue are A166D .A166G .A166P .A166S .A166T .A166V . 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.

A166T Reported Clinical Data

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

A166T 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 103.2 4.2 -8.5 0.987179487 NA

A166T 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 0.006 -2.26 probablydamaging 0.999 1.164 -0.59 -1 0.801

A166T has 40 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
133 13.1
136 13 L136P
137 11.1 I137V
139 14.7
140 10.4
141 13.1 I141N I141V
143 13.9
144 12.9
147 14.6
157 14.7
158 13.6
159 12.1 Y159C
160 10.1
161 10.1 E161K
162 8.1
163 5.4
164 7.2
165 4.1
167 4.1
168 6.3
169 4.9
170 7.1
171 8.9
172 9.7
173 10.7
174 12.2
175 13.6
197 13.8
198 13.5
200 13.5
201 9.7
202 13
204 10.5
205 10
206 14.1
207 13.5
208 10
209 14.5
222 13.3 R222Q
225 12.8 R225Q R225W