G752R Summary

SCN5A G752R was found in 12 papers (see below) with a total of 10 carriers: 8 had BrS1, 0 had LQT3, and 1 had other disease. G752R is present in 1 out of 247910 alleles in gnomAD (minor allele frequency of 0.000403%). G752R has been functionally characterized in 3 papers. Other variants at the same resdue are G752A .G752E .G752R .G752R .G752V . Given the functional data available, we estimate this variant has "Partial_LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

G752R Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1269350620031500
1210694320020100
1664339920060100
2003163420092400
2288591720120200
2436561420140001Aflutter
2002282120100200
1925120920090100
2004237420100000
2012928320100100
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G752R 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
12693506 2003 COS 6.3 30 -10 NA
32533946 2020 HEK 23.2 22.6 NA

G752R 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 -7.66 probablydamaging 0.981 0.6352 -3.37 -9 0.97

G752R has 44 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
723 14.5 I723V
725 14.3
726 9.9
727 11.9
728 12.5 V728I
729 8.9
730 7.3
731 11.2
732 10.9
733 6.1 F733L F733L F733L
734 9.9
735 12.6 A735E A735T A735V
736 12
737 12
741 14.2
743 14.4
744 13.8
745 11.5
746 11.6 E746K
747 8.9
748 6.9
749 6
750 6.2
751 3.9 V751I
753 3.7
754 5.5
755 4.9
756 5
757 7.8
758 9.5
759 9.7 I759V
760 10.6
761 13.3
762 14.8
789 14.8 V789I
792 12.3
793 14.1
795 12.7
796 11.5
799 14.2
800 14.5 R800C R800H R800L
808 12.7 R808C
811 10.3 R811H
814 11.2 R814Q