D1690N Summary

SCN5A D1690N was found in 5 papers (see below) with a total of 3 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. D1690N is present in 1 out of 251488 alleles in gnomAD (minor allele frequency of 0.000398%). D1690N has been functionally characterized in 2 papers. Other variants at the same resdue are D1690A .D1690E .D1690E .D1690G .D1690H .D1690N .D1690V .D1690Y . Given the functional data available, we estimate this variant has "Partial_LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

D1690N Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2308548320130100
2710895220160000
3023226820180000
2617311120150100
2932597620180100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D1690N 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
23085483 2013 CHO 20 4.7 3.2 NA
27108952 2016 HEK 23 7 0 NA
30232268 2018 CHO 51.6 NA

D1690N 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 0.023 -4.79 probablydamaging 1 0.3129 -0.31 2 0.838

D1690N has 50 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
324 12.5
325 13.9
326 11.9
327 13.8
329 14.6
330 14
331 10.7
332 10.8 A332T
333 7.9
334 9.2
335 11.8 C335R
336 11.9 P336L
379 11.9
382 13.1
383 9.6
384 14.9
386 14.6 G386E G386R G386R
387 13.8
1227 12.2
1228 13.3 Y1228C Y1228H
1676 14.7 M1676I M1676I M1676I
1679 14.2
1680 12 A1680T
1681 10.3 Y1681F
1682 10.6
1683 10.5
1684 5.4
1685 10.7
1686 11.7
1687 9.5
1688 6.9
1689 4.9
1691 6.1
1692 8
1693 6.4
1694 10.9
1695 8
1696 11.2
1698 12.9 A1698T
1699 9.4
1700 13.1
1702 12.7
1703 12.3
1715 14.6
1716 13.4
1719 12.5
1720 14.8
1739 14.4 R1739Q R1739W
1740 14.8 G1740R G1740R
1741 12.2 D1741N