D591N Summary

KCNH2 D591N was found in 1 paper (see below) with a total of 3 carriers: 0 had LQT2. D591N is present in 2 out of 251396 alleles in gnomAD (0.000796%). D591N has been functionally characterized in 0 papers. This residue is located in a Mild_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 8 individuals unaffected with LQT2 and 2 individuals affected with LQT2.


D591N Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
26746457 2016 1 1
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D591N 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.

PAM Score REVEL Score PROVEAN Score Polyphen2 Score BLAST-PSSM
2 0.556 -2.176 0.009 1

D591N has 34 neighbors (found in individuals) within 15 ångströms

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. NOTE: some residues appear multiple times at different distances. This results from the fact that the functional Kv11.1 channel is a homotetramer and occasionally the same residue from multiple subunits is present within the 15A window. All variants shown in the rightmost column have been observed in at least one individual in the literature or gnomAD.

ResidueNumber Distance(Å) Variants
583 11.1 I583V
583 12 I583V
584 10.1 G584C G584R G584S
584 13.7 G584C G584R G584S
585 11.4 W585C
586 9.6 L586M
587 7.5
588 5.5 N588D N588K
588 14.2 N588D N588K
589 6.5 L589P
590 3.6 G590D G590V
592 14 Q592X
592 5.4 Q592X
593 7 I593K I593R I593T I593V I593X
594 7.4
595 8.5 K595E K595N
596 6.8 P596L P596R P596S P596T
597 9.2 Y597C Y597H
603 13.2 G603D
604 11.2 G604C G604D G604S
605 10.7 P605L
606 14 S606Del S606F S606P
609 14 D609G D609N
610 13.7
613 13.6 T613A T613K T613L T613M
628 13.7 G628A G628D G628Del G628R G628S G628V
629 11.6 N629D N629I N629K N629S N629T
630 12.3 V630A V630I V630T
631 14.9 S631F
631 12.9 S631F
632 14.9 P632A P632S
633 13.5 N633D N633I N633S
633 11.1 N633D N633I N633S
634 14.3 T634A T634I T634P T634S