D785N Summary

SCN5A D785N was found in 2 papers (see below) with a total of 2 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. D785N is not present in gnomAD. D785N has been functionally characterized in 1 paper. Other variants at the same resdue are D785A .D785E .D785E .D785G .D785H .D785N .D785V .D785Y . 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.

D785N Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2458110520140200
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D785N 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 38.9 11.8 -7.1 2 NA

D785N 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 -4.95 probablydamaging 0.961 0.1205 -2.43 2 0.971

D785N has 56 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 13.4 V714A
719 13.4
720 11.2
722 14.4
723 10 I723V
724 12.4 T724I
726 13.2
727 10.9
730 13.7
756 14
757 11.8
758 12.7
759 12.1 I759V
760 8.1
761 9.9
762 11.3
763 9.8 E763K
764 5.9 M764K
765 11.1
766 13.4
767 9
768 10.5
769 14.6
770 14.6
771 12.8
773 13.6
776 8.5
777 9.9
778 13.7
779 10.3 Q779K
780 8
781 6.9
782 5.6
783 6.8
784 4.3
786 5.1
787 6.5
788 5.2
789 6.9 V789I
790 9.5
791 10.6
792 10.8
793 12.9
794 14.6
810 13.1
811 14 R811H
812 13.5
813 9.2
814 8.6 R814Q
815 11.5
816 10.8 F816Y
817 6.3
818 11.5
819 11.7
820 9.6
821 12.7