H445D Summary

SCN5A H445D was found in 4 papers (see below) with a total of 15 carriers: 1 had BrS1, 0 had LQT3, and 4 had other disease. H445D is present in 14 out of 275240 alleles in gnomAD (minor allele frequency of 0.005086%). H445D has been functionally characterized in 0 papers. Other variants at the same resdue are H445D .H445L .H445N .H445P .H445Q .H445Q .H445R .H445Y . This residue is located in a Non_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

H445D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1837860920080002AF
2281806720120003AF
2565040820150100
2808616720170001MI
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

H445D 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 0.013 -1.37 benign 0.011 1.204 -1.22 -4 0.63

H445D 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
430 14.7
431 14.2
432 13.7
433 13.2 R433C
434 12.6
435 12
436 11.4
437 10.7
438 10.1
439 9.3
440 8.5
441 7.6
442 6.6
443 5.4
444 3.8
446 3.8 E446K
447 5.4 A447G
448 6.6
449 7.6 T449A
450 8.5
451 9.3
452 10.1
453 10.7 V453M
454 11.4
455 12
456 12.6 V456M
457 13.2
458 13.7 R458C R458H
459 14.2
460 14.7