A997S Summary

SCN5A A997S was found in 3 papers (see below) with a total of 2 carriers: 0 had BrS1, 1 had LQT3, and 1 had other disease. A997S is present in 1 out of 31326 alleles in gnomAD (minor allele frequency of 0.003192%). A997S has been functionally characterized in 1 paper. Other variants at the same resdue are A997D .A997G .A997P .A997S .A997T .A997V . Given the functional data available, we estimate this variant has "GOF" 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 Mild_Hotspot region for Long QT syndrome.

A997S Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1171089220010001SIDS
1971608520090010
2954460520180001SIDS
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A997S 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
11710892 2001 HEK NA 733.3

A997S 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 0.594 -0.42 benign 0 3.271 0.24 0 0.488

A997S 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
982 14.7 C982R
983 14.2 G983D
984 13.7
985 13.2
986 12.6 R986L R986Q R986W
987 12
988 11.4 R988Q R988W
989 10.7
990 10.1
991 9.3
992 8.5
993 7.6 A993T
994 6.6
995 5.4 L995F
996 3.8
998 3.8
999 5.4
1000 6.6 p.Gln1000del
1001 7.6
1002 8.5 P1002S
1003 9.3
1004 10.1 C1004R
1005 10.7
1006 11.4
1007 12
1008 12.6 P1008S
1009 13.2
1010 13.7
1011 14.2 P1011L P1011S
1012 14.7