P468L Summary

SCN5A P468L was found in 1 paper (see below) with a total of 7 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. P468L is present in 3 out of 248632 alleles in gnomAD (minor allele frequency of 0.001207%). P468L has been functionally characterized in 1 paper. Other variants at the same resdue are P468A .P468L .P468Q .P468R .P468S .P468T . 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 Non_Hotspot region for Long QT syndrome.

P468L Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1982976620093100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

P468L 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
19829766 2009 HEK 107 -1.4 2.8 NA

P468L 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
Tolerated 0.074 -2.24 benign 0.001 2.075 0.2 -7 0.205

P468L has 30 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
453 14.7 V453M
454 14.2
455 13.7
456 13.2 V456M
457 12.6
458 12 R458C R458H
459 11.4
460 10.7
461 10.1 L461V
462 9.3 E462K
463 8.5 M463R
464 7.6
465 6.6
466 5.4 L466F L466F
467 3.8
469 3.8
470 5.4 N470K N470K
471 6.6
472 7.6
473 8.5
474 9.3 R474K
475 10.1 R475K R475S R475S
476 10.7
477 11.4
478 12
479 12.6
480 13.2 K480N K480N
481 13.7 R481Q R481W
482 14.2
483 14.7