L567Q Summary

SCN5A L567Q was found in 4 papers (see below) with a total of 9 carriers: 6 had BrS1, 0 had LQT3, and 4 had other disease. L567Q is present in 2 out of 249034 alleles in gnomAD (minor allele frequency of 0.000803%). L567Q has been functionally characterized in 1 paper. Other variants at the same resdue are L567M .L567P .L567Q .L567R .L567V . 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 Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

L567Q Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1112325120010000
1071193320001104SIDS
1107682520000500
1190104620020100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

L567Q 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
11123251 2001 HEK 65.7 6.1 -11.3 NA

L567Q 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 0.326 0.89 probablydamaging 0.966 3.294 0.51 -5 0.598

L567Q 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
552 14.7 G552R G552R G552W
553 14.2
554 13.7
555 13.2 E555K
556 12.6
557 12 H557Y
558 11.4 H558R
559 10.7 T559I
560 10.1
561 9.3
562 8.5
563 7.6
564 6.6
565 5.4
566 3.8
568 3.8 R568C R568H
569 5.4 R569Q R569W
570 6.6 T570N
571 7.6 S571I
572 8.5 A572D A572F A572S A572V
573 9.3 Q573E
574 10.1
575 10.7
576 11.4
577 12
578 12.6
579 13.2 G579R G579R
580 13.7
581 14.2 S581L
582 14.7