A286S Summary

SCN5A A286S was found in 2 papers (see below) with a total of 80 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. A286S is present in 79 out of 280724 alleles in gnomAD (minor allele frequency of 0.028142%). A286S has been functionally characterized in 1 paper. Other variants at the same resdue are A286E .A286G .A286P .A286S .A286T .A286V . 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 Non_Hotspot region for Long QT syndrome.

A286S Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2012928320101000
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A286S 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
32533946 2020 HEK 105.8 3.2 2.7 0.705128205 NA

A286S 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 0.935 -0.03 benign 0.003 3.757 -0.05 0 0.238

A286S has 13 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
281 14.4 V281M
282 8.5 R282C R282H
283 10.7
284 6.1
285 3.9
287 4
288 7.3
289 10.2 G289S
318 14.5
319 12.8 G319S
337 13.9
338 11.5
339 12.1