P773S Summary

SCN5A P773S was found in 2 papers (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. P773S is not present in gnomAD. P773S has been functionally characterized in 1 paper. Other variants at the same resdue are P773A .P773H .P773L .P773R .P773S .P773T . 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.

P773S Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

P773S 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 120.5 1.7 -3.8 1.58974359 NA

P773S 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 -7.92 possiblydamaging 0.521 0.3532 -2.23 -2 0.943

P773S has 26 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 14.1
711 13.6
714 14.3 V714A
764 11.5 M764K
765 10.8
766 12.9
767 10.4
768 5.7
769 8.2
770 8.8
771 7.2
772 3.9 D772N
774 4.4 Y774C
775 6.4
776 5.8
777 5.4
778 8.7
779 11.2 Q779K
780 13.1
782 9.8
783 10.7
785 13.6 D785N
786 11.2
787 14.7
789 15 V789I
790 15