G615E Summary

SCN5A G615E was found in 10 papers (see below) with a total of 77 carriers: 1 had BrS1, 8 had LQT3, and 3 had other disease. G615E is present in 66 out of 227496 alleles in gnomAD (minor allele frequency of 0.029011%). G615E has been functionally characterized in 1 paper. Other variants at the same resdue are G615A .G615E .G615R .G615R .G615V . Given the functional data available, we estimate this variant has "Mild_LOF" 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.

G615E Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2461399520140001irritable bowel syndrome
1199728120020001diLQT
1807106920080001SCD
1584047620050010
2363143020130010
2666966120161010
2674645720161010
2756675520160020
1971608520090050
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G615E 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
24613995 2014 HEK 36.4 5.6 3.1 72.5
11997281 2002 HEK-tSA201 93.8 0.5 2.4 NA
18071069 2008 Xeno 100 -2.6 1.7 NA

G615E 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 0.09 -2.11 probablydamaging 0.975 3.338 0.06 -4 0.626

G615E 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
600 14.7
601 14.2
602 13.7
603 13.2
604 12.6 L604V
605 12
606 11.4
607 10.7 G607V
608 10.1 D608N
609 9.3
610 8.5
611 7.6
612 6.6
613 5.4
614 3.8
616 3.8
617 5.4
618 6.6 L618F
619 7.6 L619F
620 8.5 R620C R620H
621 9.3
622 10.1
623 10.7
624 11.4 L624Q
625 12 E625D E625D
626 12.6
627 13.2 P627L
628 13.7
629 14.2
630 14.7 T630M