R535Q Summary

SCN5A R535Q was found in 2 papers (see below) with a total of 8 carriers: 0 had BrS1, 3 had LQT3, and 0 had other disease. R535Q is present in 5 out of 248026 alleles in gnomAD (minor allele frequency of 0.002016%). R535Q has been functionally characterized in 0 papers. Other variants at the same resdue are R535G .R535L .R535P .R535Q . Given the functional data available, we estimate this variant has "Mild_LOF" 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 Hotspot region for Long QT syndrome.

R535Q Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2434941820130010
1971608520090020
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R535Q 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
24349418 2013 hiPSC-CM 59.2 NA

R535Q 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
Tolerated 0.057 -2.04 probablydamaging 0.997 1.976 0.83 -2 0.655

R535Q 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
520 14.7 M520V
521 14.2 K521E
522 13.7
523 13.2 R523C R523H
524 12.6 S524Y
525 12
526 11.4 R526C R526H
527 10.7 G527R G527R
528 10.1 S528R S528R S528R
529 9.3
530 8.5 F530V
531 7.6 T531A
532 6.6 F532C F532L F532L F532L
533 5.4 R533C R533H R533S
534 3.8
536 3.8 D536H
537 5.4
538 6.6
539 7.6
540 8.5
541 9.3
542 10.1
543 10.7
544 11.4
545 12
546 12.6
547 13.2
548 13.7
549 14.2
550 14.7