E1574K Summary

SCN5A E1574K was found in 4 papers (see below) with a total of 4 carriers: 4 had BrS1, 0 had LQT3, and 0 had other disease. E1574K is not present in gnomAD. E1574K has been functionally characterized in 1 paper. Other variants at the same resdue are E1574A .E1574D .E1574D .E1574G .E1574K .E1574Q .E1574V . 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.

E1574K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1902912420090100
2694133920160100
2012928320100400
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E1574K 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 43.3 9.8 NA

E1574K 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 -3.61 probablydamaging 0.981 0.08638 -2.88 -4 0.958

E1574K has 63 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
1521 11.2
1522 13.4
1523 14.7 D1523N
1524 10.1 I1524T
1525 8.8 V1525M
1526 12.6 T1526P
1527 12.3
1528 14.8
1529 11.9
1530 6.8
1531 8.9
1532 11.8 V1532F V1532I
1533 9.9 T1533I
1534 5.9
1535 9.4
1536 13.1
1537 9.5
1538 10.1
1539 13.7 C1539Y
1540 14.2
1541 13
1566 12.7
1567 11.1
1568 9.5
1569 9
1570 7.1 p.1570_F1571insI p.I1570dup
1571 5.3
1572 6.5
1573 4.8
1575 4.2
1576 7.2
1577 6.4
1578 5.1
1579 9.4
1580 11
1581 11.4
1582 11.4
1583 14.9 R1583C R1583H
1586 9.3
1587 13.3
1589 12.5
1590 14
1591 12.6
1592 8.4
1593 12.2 I1593M
1594 12.7
1595 7
1596 9.8 F1596I
1597 12.2 V1597M
1598 10.4
1599 8.6
1600 12.4
1601 14.8 L1601H
1602 12.7
1603 13.9
1625 14.4
1626 13.1 R1626C R1626H R1626P
1628 14.4
1629 8.9 R1629G R1629Q
1630 14
1631 14.7 G1631D
1632 10 R1632C R1632H
1635 13.7