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
|| Other disease
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.
|| Cell type
|| Peak current
|| V0.5 act
|| V0.5 inact
|| Rec from inact
|| Late current
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.
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.