E1784K Summary

SCN5A E1784K was found in 51 papers (see below) with a total of 164 carriers: 31 had BrS1, 114 had LQT3, and 2 had other disease. E1784K is not present in gnomAD. E1784K has been functionally characterized in 6 papers. Other variants at the same resdue are E1784A .E1784D .E1784D .E1784G .E1784K .E1784Q .E1784V . Given the functional data available, we estimate this variant has "GOF" 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 Hotspot region for Long QT syndrome.

E1784K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2443987520140211Sino-atrial block
18451998200839380
27381756201607100
2613192420150000
2948362120180000
1072764720000000
1096195520000030
1097384920000010
1190104620020100
1287769720030030
1584047620050040
1637953920050020
1797166120081250
1845287320080011AF
1850878220080901SD
1918186720090100
2012369720100100
2054104120100080
2056648220100100
2065994620100040
2132146520110100
22360817201200130
2309806720120010
2363143020130010
2466778320150010
2476280520140040BrS (overlap), SSS
266696612016140200
2672985420160100
2692176420160900
2694092520160010
2834178120170200
2878184920171100
2901792720170000
24871449201400140
2492032320140000
2590454120150030
27566755201600700
27915266201700160
2841215820170000
2012928520100000
2018823020100000
2873407320170000
2767733420160010
2889826720170000
1037708119990040
19716085200900150
20129283201001400
1072765320000010
2932597620180400
30059973201800690
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1784K 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
24439875 2014 tsA201 39 0 -18.4 1435.7
18451998 2008 tsA201 59.6 12.5 -15 347.7
27381756 2016 tsA201 70 -11.03 NA
26131924 2015 CHO 105.8 -0.16 -16.19 405.4
29483621 2018 HEK 144.4 5.32 -11.84 49.7
28734073 2017 HEK NA NA
27677334 2016 hiPSC NA NA
28898267 2017 Oocytes NA NA
10377081 1999 Xeno NA NA -12.1 1000
10727653 2000 HEK-tSA201 0 8.8 -14.4 NA 500
32533946 2020 HEK 51.9 -5.4 0.884615385 NA

E1784K 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 -3.57 possiblydamaging 0.82 0.8009 0.04 -4 0.91

E1784K has 43 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
1488 11.6
1489 10.9 E1489D E1489D
1490 7.1
1491 10.5
1492 11.4
1493 5.9 K1493R p.K1493del
1494 9.5
1495 13.8
1496 11.4
1497 10.5
1498 13.2 M1498R M1498T
1500 13.5
1501 15 L1501V
1776 14
1777 12.4 V1777M
1778 11.8
1779 11.2 T1779M
1780 8.3
1781 8.3 E1781G
1782 7.9
1783 5.1
1785 4.3
1786 8.5 L1786Q
1787 11.2 S1787N
1790 12.9 D1790G D1790N
1791 14
1823 14.6 E1823K
1824 11
1825 13.6 L1825P
1858 11
1859 12.3
1860 13.7
1861 8.6
1862 6.4
1863 9.4
1864 10.8
1865 6
1866 7.9
1867 11.4
1868 8
1869 12.6
1870 14.8 A1870T
1874 14.5