D509A Summary

KCNH2 D509A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. D509A is not present in gnomAD. D509A has been functionally characterized in 1 paper. This residue is located in a Non_Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 9 individuals unaffected with LQT2 and 1 individuals affected with LQT2.


D509A Reported Clinical Data

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

D509A Reported Functional Data: heterozygously collected

Steady state (S.S.) and peak tail current are relative % to wildtype (100% being no different from 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. Recovery from inactivation (Rec. inact.) and deactivation time (Deactivation) are the ratio of characteristic time constants with wildtype (unitless).

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
15975984 2005 Xeno

D509A Reported Functional Data: homozygously collected

PMID Year Cell type S.S. peak current (%WT) Peak tail current (%WT) V0.5 act V0.5 inact Rec. inact. (%WT) Deactivation (%WT)
15975984 2005 Xeno 27.10 -3.20

D509A 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
-3 0.946 -7.38 0.998 -2

D509A has 16 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
453 14.1
456 14.4 D456Y
457 12.8 L457P
460 13.6 D460fsX
505 14.5 A505V
506 11.8 I506V
507 8.5 P507L P507S
508 6.3
510 4.5
520 10.9
521 10
522 11.7 G522E
523 14.5
524 11
525 11.2 K525N
528 14.3 R528P R528W R528X