K817E Summary

SCN5A K817E was found in 1 paper (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 1 had other disease. K817E is not present in gnomAD. K817E has been functionally characterized in 1 paper. Other variants at the same resdue are K817E .K817M .K817N .K817N .K817Q .K817R .K817T . 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.

K817E Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2677655520160101SSS
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

K817E 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
26776555 2016 HEK 60 24.1 0.1 NA

K817E 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 -3.96 probablydamaging 0.977 0.1358 -2.48 -4 0.964

K817E has 60 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
714 14.5 V714A
719 12.4
720 9
721 12.1
722 11.9
723 7.7 I723V
724 7.6 T724I
725 12
726 10.4
727 6.6
728 10.5 V728I
729 13.3
730 11
731 11.2
734 13.7
756 13
757 13.5
758 14.8
759 12.9 I759V
760 9.1
761 13.7
762 14.4
763 11.8 E763K
764 10.4 M764K
767 12.2
776 13.4
779 12.8 Q779K
780 10.5
781 6.5
782 9.7
783 11.7
784 6.6
785 6.3 D785N
786 11.2
787 11.3
788 8.4
789 11.6 V789I
790 14.7
791 14.2
792 13.7
810 14.5
811 13.8 R811H
812 11.5
813 9.1
814 7.8 R814Q
815 7.2
816 7.5 F816Y
818 5.3
819 6.5
820 5.8
821 6.9
822 10.4
823 12.5
824 14.1
825 10.8
826 10.8
829 12.5
1343 12.9
1344 14.4
1347 13.4