L409P Summary

SCN5A L409P was found in 3 papers (see below) with a total of 1 carrier: 0 had BrS1, 1 had LQT3, and 0 had other disease. L409P is not present in gnomAD. L409P has been functionally characterized in 0 papers. Other variants at the same resdue are L409C .L409M .L409P .L409Q .L409R .L409V . Given the functional data available, we estimate this variant has "GOF" 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.

L409P Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2206421120120010
2399504420130010
2421843720130010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

L409P 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
22064211 2012 HEK-tSA201 70 5 8 350

L409P 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 -6.87 probablydamaging 1 0.1182 -5.31 -7 0.994

L409P has 80 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
242 12.8
243 13.1
245 14.3 Q245K
246 9.9
247 12.8 V247L V247L
249 12.3
250 10.5
253 11.8
254 13.6
257 14.5
369 13.8 M369K
370 13.9 T370M
371 14.8 Q371E
400 13.8 G400E G400R G400R
401 11.9
402 12.3 F402L F402L F402L
403 12
404 9.9
405 6.8
406 5.4 N406K N406K N406S
407 7
408 5.4
410 4.3
411 6.5 V411M
412 5.3
413 6.1 A413T
414 9.2
415 10.2
416 11 Y416C
417 12.4
418 14.3
842 14.8
923 14.1
924 12.5 V924I
925 14.1
926 12.4
927 10.2 N927S
928 8.2
929 8.8
930 10.6
931 9.7
932 4.7
933 8.5
934 11
935 6.7
936 7.8
937 12.1
938 11.7
939 9.9
940 13.4
1459 14.3
1462 14.7
1463 11
1464 14.4
1466 9.5
1467 11.3
1468 14.8
1469 13.2
1470 10.2
1471 14.1
1473 14.7 F1473C
1646 12.8
1649 14
1650 13.2
1653 14.7
1764 13.2
1765 11.2
1766 14.6 M1766T M1766V
1767 12.2 Y1767C
1768 7.5 I1768V
1769 9.6
1770 12.1
1771 8.6
1772 6.3
1773 11.2
1774 12.9
1775 9.3
1776 11.2
1777 14.9 V1777M
1779 13.6 T1779M