S483A Summary

SCN5A S483A was found in 1 paper (see below) with a total of 0 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. S483A is not present in gnomAD. S483A has been functionally characterized in 1 paper. Other variants at the same resdue are S483A .S483C .S483F .S483P .S483T .S483Y . Given the functional data available, we estimate this variant has "Partial_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 Non_Hotspot region for Long QT syndrome.

S483A Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1265088620030000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

S483A 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
12650886 2003 Oocytes NA 12.57 -7.39 NA

S483A 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 -1.93 possiblydamaging 0.768 0.6868 -0.11 0 0.55

S483A 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
468 14.7 P468L
469 14.2
470 13.7 N470K N470K
471 13.2
472 12.6
473 12
474 11.4 R474K
475 10.7 R475K R475S R475S
476 10.1
477 9.3
478 8.5
479 7.6
480 6.6 K480N K480N
481 5.4 R481Q R481W
482 3.8
484 3.8
485 5.4
486 6.6
487 7.6
488 8.5
489 9.3
490 10.1
491 10.7
492 11.4
493 12 R493K
494 12.6
495 13.2
496 13.7
497 14.2
498 14.7