A1330P Summary

SCN5A A1330P was found in 4 papers (see below) with a total of 1 carrier: 0 had BrS1, 1 had LQT3, and 1 had other disease. A1330P is not present in gnomAD. A1330P has been functionally characterized in 3 papers. Other variants at the same resdue are A1330D .A1330G .A1330P .A1330S .A1330T .A1330V . 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 Hotspot region for Long QT syndrome.

A1330P Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1625401220060000
1153556020010000
1153557320010011SIDS
1603927120050000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

A1330P 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
16254012 2006 HEK 100 NA
11535573 2001 HEK NA -1.5 8.3 126.7
16039271 2005 HEK NA NA

A1330P 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 -4.87 probablydamaging 1 0.1724 -4 -2 0.967

A1330P has 48 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
944 13.4
1320 14.6 M1320I M1320I M1320I
1322 12.4
1323 10.8
1324 9.9
1325 9.3 N1325S
1326 5.8
1327 5.8
1328 5.9
1329 3.3 G1329S
1331 4.1
1332 5 P1332L
1333 4.8
1334 5.3 I1334V
1335 8.3 M1335R
1336 9.8
1337 10.1
1338 11.3 L1338V
1339 14.7 p.L1339del
1464 12.5
1465 9.6
1466 11.3
1467 10.6
1468 7.2
1469 7
1470 11
1471 10.2
1472 6.1 p.N1472del
1473 9.3 F1473C
1474 13
1475 11.6
1476 10.6 Q1476R
1477 14.5
1479 13.1
1660 14.6 I1660V
1663 14.5
1757 11.3
1758 11.3 p.I1758del
1759 14
1761 11.6 L1761H
1762 8.1 I1762M
1763 11.2 V1763M
1764 14
1765 11.5
1766 9.2 M1766T M1766V
1768 14.5 I1768V
1769 12.6
1770 14.7