P637A Summary

SCN5A P637A was found in 1 paper (see below) with a total of 0 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. P637A is not present in gnomAD. P637A has been functionally characterized in 1 paper. Other variants at the same resdue are P637A .P637L .P637Q .P637R .P637S .P637T . This residue is located in a Non_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

P637A Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2973450520180000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

P637A 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
29734505 2018 HEK NA 1.3 3.5 NA

P637A 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 0.756 -0.11 benign 0.005 3.562 -1.35 -2 0.456

P637A 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
622 14.7
623 14.2
624 13.7 L624Q
625 13.2 E625D E625D
626 12.6
627 12 P627L
628 11.4
629 10.7
630 10.1 T630M
631 9.3
632 8.5 T632M
633 7.6
634 6.6 S634L
635 5.4
636 3.8
638 3.8
639 5.4 G639R G639R
640 6.6 P640A
641 7.6
642 8.5
643 9.3
644 10.1
645 10.7
646 11.4
647 12 A647D A647S A647V
648 12.6 P648L
649 13.2 C649Y
650 13.7
651 14.2
652 14.7