N592K Summary

SCN5A N592K was found in 3 papers (see below) with a total of 11 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. N592K is present in 8 out of 247882 alleles in gnomAD (minor allele frequency of 0.003227%). N592K has been functionally characterized in 1 paper. Other variants at the same resdue are N592D .N592H .N592I .N592K .N592K .N592S .N592T .N592Y . Given the functional data available, we estimate this variant has "Partial_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 Non_Hotspot region for Long QT syndrome.

N592K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2446357820141100
2615475420150100
2012928320101000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

N592K 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
24463578 2014 HEK 16.7 3.2 1.2 NA

N592K 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
Damaging 0.03 -2.54 possiblydamaging 0.684 2.26 -0.28 -1 0.821

N592K 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
577 14.7
578 14.2
579 13.7 G579R G579R
580 13.2
581 12.6 S581L
582 12
583 11.4
584 10.7 G584R
585 10.1
586 9.3 A586T
587 8.5
588 7.6
589 6.6
590 5.4
591 3.8
593 3.8
594 5.4
595 6.6
596 7.6
597 8.5
598 9.3
599 10.1 G599R G599R
600 10.7
601 11.4
602 12
603 12.6
604 13.2 L604V
605 13.7
606 14.2
607 14.7 G607V