R340W Summary

SCN5A R340W was found in 6 papers (see below) with a total of 9 carriers: 0 had BrS1, 7 had LQT3, and 0 had other disease. R340W is present in 2 out of 279848 alleles in gnomAD (minor allele frequency of 0.000715%). R340W has been functionally characterized in 0 papers. Other variants at the same resdue are R340G .R340L .R340P .R340Q .R340W . This residue is located in a Non_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

R340W Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1882242520080010
2460699520140010
2901792720170000
2756675520160070
1971608520090010
3005997320180010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R340W 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 0.126 -1.72 probablydamaging 0.999 3.759 0.43 -2 0.684

R340W 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