D1714G Summary

SCN5A D1714G was found in 6 papers (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. D1714G is not present in gnomAD. D1714G has been functionally characterized in 1 paper. Other variants at the same resdue are D1714A .D1714E .D1714E .D1714G .D1714H .D1714N .D1714V .D1714Y . 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.

D1714G Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1626637020050100
2127319520110100
1925120920090100
2039006720100000
1626636620050000
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D1714G 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
16266370 2005 HEK 20.8 1.9 1.9 NA

D1714G 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 0.002 -5.95 probablydamaging 1 0.5299 -3.31 -3 0.958

D1714G has 66 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
373 12.9
374 14.9
375 10.7
376 13.8 R376H
379 14.2
898 13.9
1360 14.5
1398 11.5 V1398M
1399 8.8
1400 7.8
1401 12.2
1402 14.3
1406 14.8 G1406E G1406R G1406R
1407 12.7
1408 13.2 G1408R G1408R
1409 14
1410 9.8
1411 9.3
1412 12.5
1413 10.3
1414 6
1415 10.7
1416 12.3
1417 10.1
1418 11.9
1419 7.2
1420 5.8 G1420R G1420V
1421 10.4
1422 11.4
1423 9.1
1424 9.4
1425 13.9
1427 14.2
1685 10.9
1686 8.4
1687 9.6
1688 11.9
1692 14.9
1703 13.2
1704 14.9
1706 11.9
1707 11.1
1709 14 T1709M
1710 10.6 S1710L
1711 9.4
1712 5.9 G1712S
1713 7.1
1715 4.1
1716 6.7
1717 5.2
1718 5.9
1719 8.7
1720 10
1721 9.6
1722 13.8 N1722D
1723 13.5 T1723N
1744 14 S1744I
1745 14.2
1748 11.7
1749 11.9
1751 13.9
1752 9.6
1753 12.7
1755 14.5
1756 12.4
1760 14.8