R568H Summary

SCN5A R568H was found in 2 papers (see below) with a total of 10 carriers: 0 had BrS1, 1 had LQT3, and 0 had other disease. R568H is present in 6 out of 280398 alleles in gnomAD (minor allele frequency of 0.00214%). R568H has been functionally characterized in 0 papers. Other variants at the same resdue are R568C .R568G .R568H .R568L .R568P .R568S . Given the functional data available, we estimate this variant has "GOF" 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.

R568H Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2728706820162010
2012928320101000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R568H 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
27287068 2016 Oocytes 125 NA

R568H 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 0.021 -3.39 benign 0.004 3.09 1.27 -2 0.637

R568H 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
553 14.7
554 14.2
555 13.7 E555K
556 13.2
557 12.6 H557Y
558 12 H558R
559 11.4 T559I
560 10.7
561 10.1
562 9.3
563 8.5
564 7.6
565 6.6
566 5.4
567 3.8 L567Q
569 3.8 R569Q R569W
570 5.4 T570N
571 6.6 S571I
572 7.6 A572D A572F A572S A572V
573 8.5 Q573E
574 9.3
575 10.1
576 10.7
577 11.4
578 12
579 12.6 G579R G579R
580 13.2
581 13.7 S581L
582 14.2
583 14.7