A1680T Summary

SCN5A A1680T was found in 9 papers (see below) with a total of 18 carriers: 4 had BrS1, 1 had LQT3, and 2 had other disease. A1680T is present in 13 out of 282862 alleles in gnomAD (minor allele frequency of 0.004596%). A1680T has been functionally characterized in 1 paper. Other variants at the same resdue are A1680D .A1680G .A1680P .A1680S .A1680T .A1680V . 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.

A1680T Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1671270220060001Sudden adult death syndrome
1850878220080101SD
1956456120090100
2363143020130010
2674645720160001AF, BBB
2012928320100100
2012928320100100
3025403920180100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A1680T 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 89.5 -5.3 -1.2 0.871794872 NA

A1680T 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 -3.44 probablydamaging 1 0.5955 -3.34 -1 0.889

A1680T 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
1223 14.5
1225 11.9 E1225K
1226 8.1
1227 7
1228 11.8 Y1228C Y1228H
1229 12.6
1230 13.9 E1230K
1300 12.5
1301 12.5
1304 14.9 T1304M
1672 11.5 S1672Y
1673 11.9
1674 11.7 F1674V
1675 8
1676 7 M1676I M1676I M1676I
1677 6.7
1678 7.3 N1678S
1679 5.6
1681 4.5 Y1681F
1682 5.2
1683 9.4
1684 12.2
1685 13.7
1687 14.7
1688 11.3
1689 14.6
1690 12 D1690N
1691 14.6
1692 14.1
1693 8.5
1694 6.8
1695 6
1696 9.9
1697 13.5
1698 13.8 A1698T
1699 11.7
1700 11.2
1703 13.2
1716 13.7
1717 15
1719 11.8
1720 10.1
1721 13.7
1722 14.5 N1722D
1731 13.6
1732 11.3
1734 14.1
1738 12.9
1739 10.7 R1739Q R1739W
1740 6.9 G1740R G1740R
1741 7.8 D1741N
1742 9.2
1743 8.7 G1743E G1743R G1743R
1744 9.7 S1744I
1745 13.5
1747 11.7 V1747M
1748 12.9
1751 13
1752 14.9