D536H Summary

SCN5A D536H was found in 1 paper (see below) with a total of 2 carriers: 0 had BrS1, 1 had LQT3, and 0 had other disease. D536H is present in 1 out of 248210 alleles in gnomAD (minor allele frequency of 0.000403%). D536H has been functionally characterized in 0 papers. Other variants at the same resdue are D536A .D536E .D536E .D536G .D536H .D536N .D536V .D536Y . This residue is located in a Non_Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

D536H Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2747118820160010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D536H 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
Damaging 0.001 -5.13 probablydamaging 0.998 1.874 -1.53 -4 0.676

D536H 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
521 14.7 K521E
522 14.2
523 13.7 R523C R523H
524 13.2 S524Y
525 12.6
526 12 R526C R526H
527 11.4 G527R G527R
528 10.7 S528R S528R S528R
529 10.1
530 9.3 F530V
531 8.5 T531A
532 7.6 F532C F532L F532L F532L
533 6.6 R533C R533H R533S
534 5.4
535 3.8 R535Q
537 3.8
538 5.4
539 6.6
540 7.6
541 8.5
542 9.3
543 10.1
544 10.7
545 11.4
546 12
547 12.6
548 13.2
549 13.7
550 14.2
551 14.7 A551T A551V