E161K Summary

SCN5A E161K was found in 15 papers (see below) with a total of 13 carriers: 11 had BrS1, 1 had LQT3, and 2 had other disease. E161K is present in 1 out of 240992 alleles in gnomAD (minor allele frequency of 0.000415%). E161K has been functionally characterized in 3 papers. Other variants at the same resdue are E161A .E161D .E161D .E161G .E161K .E161Q .E161V . 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.

E161K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2038465120100000
1591088120050902SSS, conduction disease
1210694320020100
16764707200601000
1984392120090100
2003163420094700
2038677020100010AV block
2127319520110800
2053975720100000
1925120920090100
1587817220050000
2012928320100100
2012928320100100
2957414020180100
3005997320180020
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E161K 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
20384651 2010 HEK 23.5 19.1 1.9 NA
15910881 2005 tsA201 40 11.9 0.9 NA

E161K 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 -3.45 probablydamaging 0.999 0.533 -2.88 -4 0.961

E161K has 49 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
140 11.6
141 12.8 I141N I141V
143 11.3
144 8.3
145 12.4
146 12.5 V146A V146M
147 7
148 9.5
149 12.7
150 12.1
151 9
152 14.6 D152N
153 14.6
154 13
155 11.4
156 8.9
157 6.6
158 5.6
159 7.4 Y159C
160 4.9
162 5.2
163 7.2
164 6.1
165 7.1
166 10.1 A166T
167 11.2
168 10.4
169 13.1
200 13.2
201 12.2
202 14.8
203 13.3
204 8.8
205 12.3
206 12.8
207 9.2
208 8.1
209 13.6
210 12.7
212 13.7
216 14.9 S216L
218 12.4
219 9.1 R219C
220 14.1 T220I
222 7.8 R222Q
223 12.9 V223L
225 13.2 R225Q R225W
855 14.6
859 13.5