F816Y Summary

SCN5A F816Y was found in 2 papers (see below) with a total of 3 carriers: 0 had BrS1, 1 had LQT3, and 1 had other disease. F816Y is not present in gnomAD. F816Y has been functionally characterized in 0 papers. Other variants at the same resdue are F816C .F816I .F816L .F816L .F816L .F816S .F816V .F816Y . 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.

F816Y Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2728706820162001RBBB
1971608520090010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

F816Y 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
27287068 2016 Oocytes 120 NA

F816Y 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 -2.97 probablydamaging 0.993 0.4097 -1.26 2 0.976

F816Y has 59 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 14.7 I723V
724 13.4 T724I
727 10.8
728 13.2 V728I
730 12.7
731 11.1
734 12.3
760 14.2
780 12.4
781 9.4
782 14.4
783 13.6
784 7.7
785 10.8 D785N
786 14.1
787 11.6
788 10
789 14.5 V789I
791 13.6
792 14.7
809 11.6
810 11.1
811 12.5 R811H
812 7.1
813 5.6
814 8.9 R814Q
815 4.5
817 7.5
818 7.2
819 6.7
820 10.5
821 11
822 11.6
823 13.9
824 13.2
825 8.9
826 11.2
827 14.2
828 11.3
829 9
830 14.7
832 12.1
833 13.8 G833R G833R
1339 13.4 p.L1339del
1340 11.4 V1340I
1341 13.6
1342 13.2
1343 8.8
1344 8.1
1345 13.8 W1345C W1345C
1346 11 L1346P
1347 7.3
1348 10.8
1349 13.6
1350 12.2
1351 11.9
1452 14.3
1456 11.8
1460 14.6