R814Q Summary

SCN5A R814Q was found in 7 papers (see below) with a total of 22 carriers: 5 had BrS1, 2 had LQT3, and 0 had other disease. R814Q is present in 7 out of 279186 alleles in gnomAD (minor allele frequency of 0.002507%). R814Q has been functionally characterized in 1 paper. Other variants at the same resdue are R814G .R814L .R814P .R814Q .R814W . 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.

R814Q Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1744274620077300
2332162020130100
2666966120161020
2834178120170100
2932597620180200
3005997320180030
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R814Q 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
32533946 2020 HEK 117.2 -2.1 -0.2 0.987179487 NA

R814Q 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 -3.97 probablydamaging 0.999 0.08529 -2.66 -2 0.967

R814Q has 69 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
720 14.5
722 14.3
723 10.6 I723V
724 11.4 T724I
725 13.8
726 9.7
727 6.8
728 10.5 V728I
729 11.1
730 6.1
731 8.2
732 12.1
733 10.9 F733L F733L F733L
734 8
735 13 A735E A735T A735V
737 14
749 13.6
750 14.1
751 14.7 V751I
752 11.2 G752R G752R
753 8.9
754 12.4
755 12.1
756 8.7
757 8
758 11
759 10.7 I759V
760 6.7
761 11.1
762 13.5
763 12.9 E763K
764 11.6 M764K
781 12.8
782 14.2
783 14.3
784 9.2
785 8.6 D785N
786 11.2
787 10.2
788 5.5
789 8.4 V789I
790 11.4
791 9.3
792 7.5
793 11.6
794 13.1
795 10.7
796 12.3
806 14.4
807 11.9
808 11 R808C
809 10
810 9.1
811 6.2 R811H
812 6.9
813 6.1
815 6.5
816 8.9 F816Y
817 7.8
818 9.6
819 12.6
820 13.5
821 13.6
1343 14.2
1346 13.8 L1346P
1347 11.4
1350 11.8
1351 13.4
1354 13.7