A572D Summary

SCN5A A572D was found in 16 papers (see below) with a total of 1465 carriers: 1 had BrS1, 5 had LQT3, and 9 had other disease. A572D is present in 1451 out of 280372 alleles in gnomAD (minor allele frequency of 0.517527%). A572D has been functionally characterized in 2 papers. Other variants at the same resdue are A572D .A572F .A572G .A572P .A572S .A572T .A572V . 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.

A572D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2300844120120000
1807106920080001SCD
2728706820160001atrial tachycardia
1282070420032010
1584047620050030
1716106420060010
1941232820080001DCM
2087508020110001SUDEP
2281806720121002AF
2516354620150001DCM
2682036520160001PCCD
2878133020175100
2040345920100000
2724397020160000
2045166720100000
2967259820180001SUDS
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A572D 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 -15 NA
18071069 2008 Xeno 100 -2.5 0.8 NA
27287068 2016 Oocytes 155 NA

A572D 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 0.426 -0.35 benign 0.055 2.065 -0.16 -3 0

A572D 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
557 14.7 H557Y
558 14.2 H558R
559 13.7 T559I
560 13.2
561 12.6
562 12
563 11.4
564 10.7
565 10.1
566 9.3
567 8.5 L567Q
568 7.6 R568C R568H
569 6.6 R569Q R569W
570 5.4 T570N
571 3.8 S571I
573 3.8 Q573E
574 5.4
575 6.6
576 7.6
577 8.5
578 9.3
579 10.1 G579R G579R
580 10.7
581 11.4 S581L
582 12
583 12.6
584 13.2 G584R
585 13.7
586 14.2 A586T
587 14.7