N70K Summary

SCN5A N70K was found in 3 papers (see below) with a total of 12 carriers: 1 had BrS1, 0 had LQT3, and 1 had other disease. N70K is present in 11 out of 247524 alleles in gnomAD (minor allele frequency of 0.004444%). N70K has been functionally characterized in 1 paper. Other variants at the same resdue are N70D .N70H .N70I .N70K .N70K .N70S .N70T .N70Y . 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 Non_Hotspot region for Long QT syndrome.

N70K Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2457316420140000
2516354620150001DCM
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

N70K 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
24573164 2014 HEK 100 -0.14 NA

N70K 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 0.001 -1.91 probablydamaging 0.985 1.096 0.43 -1 0.421

N70K 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
55 14.7
56 14.2
57 13.7
58 13.2
59 12.6
60 12 A60P
61 11.4
62 10.7
63 10.1 K63N K63N
64 9.3
65 8.5
66 7.6
67 6.6
68 5.4
69 3.8 G69D
71 3.8
72 5.4
73 6.6
74 7.6 E74D E74D
75 8.5
76 9.3
77 10.1
78 10.7
79 11.4 P79A
80 12
81 12.6
82 13.2 D82E D82E
83 13.7
84 14.2 D84G D84N
85 14.7