R340Q Summary

SCN5A R340Q was found in 5 papers (see below) with a total of 22 carriers: 0 had BrS1, 1 had LQT3, and 2 had other disease. R340Q is present in 21 out of 279838 alleles in gnomAD (minor allele frequency of 0.007504%). R340Q has been functionally characterized in 1 paper. Other variants at the same resdue are R340G .R340L .R340P .R340Q .R340W . 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 Hotspot region for Long QT syndrome.

R340Q Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2268511320120001AF
1517642520040010
2130664220110001AF
2414488320140001AF
2463177520140001SD
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R340Q 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
22685113 2012 HEK 85.7 -6.2 -5.5 NA

R340Q 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 0.692 -0.21 probablydamaging 0.984 3.759 0.59 -2 0.581

R340Q 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
278 11
279 10.7
280 8.2
281 5.8 V281M
282 9 R282C R282H
283 5.4
284 10.1
285 13.6
317 14
318 14.9
319 12.5 G319S
320 12.1 T320N
321 14.5
323 13.5
325 13.8
326 10.6
327 10.5
328 10.9
334 12.3
335 9 C335R
336 9.9 P336L
337 10.6
338 6.7
339 7.5
341 6.1 C341Y
342 5.9
343 11.9
344 11.5
345 14.5
384 14.5