D772N Summary

SCN5A D772N was found in 4 papers (see below) with a total of 7 carriers: 1 had BrS1, 1 had LQT3, and 1 had other disease. D772N is present in 5 out of 249248 alleles in gnomAD (minor allele frequency of 0.002006%). D772N has been functionally characterized in 1 paper. Other variants at the same resdue are D772A .D772E .D772E .D772G .D772H .D772N .D772V .D772Y . 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 Mild_Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

D772N Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2357158620130001stillbirth, SUDS
1971608520090010
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D772N 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
32533946 2020 HEK 105.3 -6.2 -0.7 1.102564103 NA

D772N 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 0.002 -4.44 possiblydamaging 0.924 0.7095 -1.74 2 0.775

D772N has 22 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
710 12.1
711 10.6
714 12.7 V714A
715 14.5
764 12.9 M764K
765 11.8
766 12.5
767 10.3
768 6.9
769 7.3
770 6.6
771 5.4
773 3.9
774 5.3 Y774C
775 4.8
776 7.4
777 8.6
778 9.5
779 12.2 Q779K
782 11.5
783 13.6
786 14.2