Q750R Summary

SCN5A Q750R was found in 2 papers (see below) with a total of 1 carrier: 0 had BrS1, 1 had LQT3, and 0 had other disease. Q750R is not present in gnomAD. Q750R has been functionally characterized in 1 paper. Other variants at the same resdue are Q750E .Q750H .Q750H .Q750K .Q750L .Q750P .Q750R . 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 Mild_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

Q750R Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2590454120150000
1971608520090010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

Q750R 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
25904541 2015 HEK 48 3 -2 114

Q750R 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 0.019 -1.38 benign 0.049 2.693 -0.12 -2 0.633

Q750R has 41 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
729 14.6
730 11.7
732 14.9
733 10 F733L F733L F733L
734 11.8
735 14.5 A735E A735T A735V
736 12.6
737 11
741 11.1
742 12.8
743 11.2
744 12.4
745 10.9
746 7.6 E746K
747 5.9
748 8
749 5.8
751 4.8 V751I
752 6.2 G752R G752R
753 5.4
754 5.5
755 9.2
756 10.6
757 10.3
758 12.7
759 14.5 I759V
760 14.8
792 12.5
793 13.7
795 10.3
796 9
797 12.4 G797V
798 13.7
799 9.3
800 10.3 R800C R800H R800L
802 14.4
807 14.9
808 10.2 R808C
811 10.2 R811H
814 14.1 R814Q
1354 13.6