V714A Summary

SCN5A V714A was found in 1 paper (see below) with a total of 16 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. V714A is present in 16 out of 280688 alleles in gnomAD (minor allele frequency of 0.0057%). V714A has been functionally characterized in 1 paper. Other variants at the same resdue are V714A .V714D .V714F .V714G .V714I .V714L . 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 Non_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

V714A Reported Clinical Data

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

V714A 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 101 6.2 4.9 0.551282051 NA

V714A 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 0.001 -3.8 benign 0.049 0.693 -0.89 -2 0.851

V714A has 37 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
710 6.3
711 6.1
712 6.6
713 4.4
715 4.9
716 5.7
717 9.1 P717L
718 10
719 6.4
720 7.5
721 11.9
722 11.7
723 10.8 I723V
724 13.9 T724I
759 14.7 I759V
760 14.6
762 12.1
763 8.8 E763K
764 10.3 M764K
765 12
766 9.4
767 5.8
768 11
769 10.9
770 7.4
771 7.5
772 12.7 D772N
773 14.3
775 13.6
776 10.7
777 15
779 13.2 Q779K
781 14.6
782 11.2
785 13.4 D785N
817 14.5
820 13.4