P627L Summary

SCN5A P627L was found in 3 papers (see below) with a total of 5 carriers: 0 had BrS1, 2 had LQT3, and 0 had other disease. P627L is present in 3 out of 176382 alleles in gnomAD (minor allele frequency of 0.001701%). P627L has been functionally characterized in 1 paper. Other variants at the same resdue are P627A .P627L .P627Q .P627R .P627S .P627T . 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 Mild_Hotspot region for Long QT syndrome.

P627L Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2590454120150000
2236081720120010
2756675520160020
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

P627L 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
25904541 2015 HEK 88 -1 1 82

P627L 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 0.121 -3.22 probablydamaging 0.998 1.849 -0.68 -7 0.503

P627L 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
612 14.7
613 14.2
614 13.7
615 13.2 G615E
616 12.6
617 12
618 11.4 L618F
619 10.7 L619F
620 10.1 R620C R620H
621 9.3
622 8.5
623 7.6
624 6.6 L624Q
625 5.4 E625D E625D
626 3.8
628 3.8
629 5.4
630 6.6 T630M
631 7.6
632 8.5 T632M
633 9.3
634 10.1 S634L
635 10.7
636 11.4
637 12
638 12.6
639 13.2 G639R G639R
640 13.7 P640A
641 14.2
642 14.7