A1746V Summary

SCN5A A1746V was found in 1 paper (see below) with a total of 15 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. A1746V is present in 15 out of 282592 alleles in gnomAD (minor allele frequency of 0.005308%). A1746V has been functionally characterized in 1 paper. Other variants at the same resdue are A1746D .A1746G .A1746P .A1746S .A1746T .A1746V . 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 Mild_Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

A1746V 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.

A1746V 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 89.4 1.4 3.3 1.102564103 NA

A1746V 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 0.013 -2.99 possiblydamaging 0.776 1.91 0.2 -2 0.723

A1746V 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
1399 14.8
1404 14.8
1406 12 G1406E G1406R G1406R
1407 12.8
1409 13.9
1410 11.4
1671 14.5
1674 12.5 F1674V
1675 12.7
1677 13.9
1678 10.1 N1678S
1679 11
1682 13.9
1716 14.8
1717 10.8
1718 12.8
1719 13.3
1720 9.2
1721 7.8
1722 8.6 N1722D
1723 11.7 T1723N
1724 12.6
1725 14.5 P1725L
1728 14.2
1742 12.7
1743 9.7 G1743E G1743R G1743R
1744 6.4 S1744I
1745 3.9
1747 3.9 V1747M
1748 5.2
1749 4.8
1750 5.5
1751 9.4
1752 10.4
1753 10
1754 11.6
1756 14.7