G552R Summary

SCN5A G552R was found in 2 papers (see below) with a total of 6 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. G552R is present in 5 out of 249050 alleles in gnomAD (minor allele frequency of 0.002008%). G552R has been functionally characterized in 1 paper. Other variants at the same resdue are G552A .G552E .G552R .G552R .G552V .G552W . 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 Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

G552R Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2457316420140000
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G552R 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
24573164 2014 HEK 97.5 -1.75 NA

G552R 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 0.033 -2.59 probablydamaging 1 3.257 0.06 -9 0.814

G552R 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
537 14.7
538 14.2
539 13.7
540 13.2
541 12.6
542 12
543 11.4
544 10.7
545 10.1
546 9.3
547 8.5
548 7.6
549 6.6
550 5.4
551 3.8 A551T A551V
553 3.8
554 5.4
555 6.6 E555K
556 7.6
557 8.5 H557Y
558 9.3 H558R
559 10.1 T559I
560 10.7
561 11.4
562 12
563 12.6
564 13.2
565 13.7
566 14.2
567 14.7 L567Q