F532C Summary

SCN5A F532C was found in 7 papers (see below) with a total of 12 carriers: 4 had BrS1, 3 had LQT3, and 2 had other disease. F532C is present in 4 out of 247568 alleles in gnomAD (minor allele frequency of 0.001616%). F532C has been functionally characterized in 0 papers. Other variants at the same resdue are F532C .F532I .F532L .F532L .F532L .F532S .F532V .F532Y . 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 Non_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

F532C Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1859657020080001SIDS
1599617020050001AF, AT, MS
2054104120100030
2834178120170100
2906269520170200
2674645720161000
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

F532C 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
18596570 2008 tsA201 100 0 0 NA

F532C 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 -4.75 probablydamaging 0.999 1.617 0.15 -13 0.89

F532C has 30 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
517 14.7
518 14.2
519 13.7
520 13.2 M520V
521 12.6 K521E
522 12
523 11.4 R523C R523H
524 10.7 S524Y
525 10.1
526 9.3 R526C R526H
527 8.5 G527R G527R
528 7.6 S528R S528R S528R
529 6.6
530 5.4 F530V
531 3.8 T531A
533 3.8 R533C R533H R533S
534 5.4
535 6.6 R535Q
536 7.6 D536H
537 8.5
538 9.3
539 10.1
540 10.7
541 11.4
542 12
543 12.6
544 13.2
545 13.7
546 14.2
547 14.7