K407D Summary

KCNH2 K407D was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. K407D is not present in gnomAD. K407D has been functionally characterized in 1 paper. This residue is located in a Hotspot region for LQT2.

In silico predictions, functional data (if available), and location in structure are equivalent to observing 6 individuals unaffected with LQT2 and 4 individuals affected with LQT2.


K407D 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.

K407D 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)
16550488 2005 Xeno

K407D 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)
16550488 2005 Xeno -43.08

K407D 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
-4 NA NA NA NA

K407D has 46 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
3 10.9
5 13.6
398 14.7 W398L W398X
399 12.5
400 8 I400N
401 7.9
402 7.4 H402R
403 9.3
404 6
405 7.4
406 5.4
408 4.8
409 7 V409L V409M
410 5.6 W410X
411 5.2
412 9.9 W412X
413 10 L413P
414 9.1 I414fsX
415 12.4
416 14.6
417 13.9
462 12.4 M462Ins
463 13.5 F463L
465 11.6
466 9 D466E
467 12.7
468 12.6 L468F L468R L468X
469 7.6
470 8.7 N470D
471 13.2 F471X
472 12.7 R472C R472X
473 7.7 T473P
474 9.2 T474I
475 13 Y475C Y475Del
476 13.6 V476I
489 14.5 I489F I489I
493 14.1 Y493C Y493F Y493H Y493Ins
534 11.7 R534C
535 13.1 V535M
537 11.9 R537W
538 8.9
539 14.3
540 12.5 D540fsX
541 7.8 R541C R541H
542 11
544 13.8 E544A E544fsX