Q573E Summary

SCN5A Q573E was found in 2 papers (see below) with a total of 3 carriers: 0 had BrS1, 1 had LQT3, and 0 had other disease. Q573E is present in 2 out of 280386 alleles in gnomAD (minor allele frequency of 0.000713%). Q573E has been functionally characterized in 0 papers. Other variants at the same resdue are Q573E .Q573H .Q573H .Q573K .Q573L .Q573P .Q573R . 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 Mild_Hotspot region for Long QT syndrome.

Q573E Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2300844120120000
1641494420050010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

Q573E 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
23008441 2012 HEK 100 -12 NA

Q573E 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 0.455 -1.05 benign 0.047 3.528 0.25 1 0.565

Q573E 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
558 14.7 H558R
559 14.2 T559I
560 13.7
561 13.2
562 12.6
563 12
564 11.4
565 10.7
566 10.1
567 9.3 L567Q
568 8.5 R568C R568H
569 7.6 R569Q R569W
570 6.6 T570N
571 5.4 S571I
572 3.8 A572D A572F A572S A572V
574 3.8
575 5.4
576 6.6
577 7.6
578 8.5
579 9.3 G579R G579R
580 10.1
581 10.7 S581L
582 11.4
583 12
584 12.6 G584R
585 13.2
586 13.7 A586T
587 14.2
588 14.7