C981F Summary

SCN5A C981F was found in 2 papers (see below) with a total of 1 carrier: 0 had BrS1, 1 had LQT3, and 0 had other disease. C981F is not present in gnomAD. C981F has been functionally characterized in 1 paper. Other variants at the same resdue are C981A .C981F .C981G .C981R .C981S .C981S .C981W .C981Y . This residue is located in a Non_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

C981F Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2733759020160000
1971608520090010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

C981F 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
27337590 2016 HEK NA -3.9 -9.4 NA

C981F 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
Tolerated 0.334 -1.08 probablydamaging 0.994 3.598 0 -13 0.504

C981F has 30 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
966 14.7
967 14.2
968 13.7
969 13.2 G969C
970 12.6
971 12 R971C R971H
972 11.4
973 10.7
974 10.1
975 9.3 R975Q R975W
976 8.5
977 7.6
978 6.6
979 5.4
980 3.8
982 3.8 C982R
983 5.4 G983D
984 6.6
985 7.6
986 8.5 R986L R986Q R986W
987 9.3
988 10.1 R988Q R988W
989 10.7
990 11.4
991 12
992 12.6
993 13.2 A993T
994 13.7
995 14.2 L995F
996 14.7