M764K Summary

SCN5A M764K was found in 2 papers (see below) with a total of 2 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. M764K is not present in gnomAD. M764K has been functionally characterized in 1 paper. Other variants at the same resdue are M764I .M764I .M764I .M764K .M764L .M764L .M764R .M764T .M764V . 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 Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

M764K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
3037118920180200
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

M764K 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 77.5 3.9 3 0.717948718 NA

M764K 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 -5.94 benign 0.285 0.344 -3.04 -2 0.951

M764K has 52 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
710 11.4
711 14.2
713 12.3
714 10.3 V714A
716 14.4
719 10.8
720 10.5
722 12.8
723 9.3 I723V
724 13.5 T724I
726 12.8
727 12.7
755 14.6
756 13.1
757 10.7
758 9.6
759 9.2 I759V
760 7
761 6.2
762 6.1
763 5.2 E763K
765 5.5
766 7.5
767 4.9
768 6.4
769 9.5
770 10.2
771 9.8
772 12.9 D772N
773 11.5
776 7.4
777 10.3
778 14.7
779 12.5 Q779K
780 12.1
781 11.7
782 7.4
783 10.3
784 10.2
785 5.9 D785N
786 6.8
787 10.4
788 8.8
789 7 V789I
790 10.5
791 13.2
792 11.7
793 12.2
813 14.2
814 11.6 R814Q
817 10.4
820 13.1