D342V Summary

KCNH2 D342V was found in 2 papers (see below) with a total of 1 carrier: 0 had LQT2. D342V is not present in gnomAD. D342V has been functionally characterized in 1 paper. Given the functional data available, we estimate this variant has "Dominant LOF" 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 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.


D342V Reported Clinical Data

PMID Year Carriers Unaffected LQT2 Other disease
19843919 2009 1 1
Japan Cohort 2020 1 1 0
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

D342V 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)
19843919 2009 CHO 46.2

D342V 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)
19843919 2009 CHO 0

D342V 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
-8 0.885 -4.871 0.996 -4

D342V has 30 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
327 14.7 Y327H
328 14.2 R328C R328fsX R328H
329 13.7
330 13.2 I330V
331 12.6 S331N S331T
332 12
333 11.4
334 10.7 P334L
335 10.1 Q335X
336 9.3
337 8.5 T337S T337X
338 7.6
339 6.6
340 5.4 F340L
341 3.8
343 3.8 L343fsX
344 5.4
345 6.6 G345S
346 7.6 D346E D346N D346Y
347 8.5 P347S
348 9.3
349 10.1
350 10.7
351 11.4 S351L
352 12
353 12.6 T353S
354 13.2
355 13.7 D355G
356 14.2 R356C R356H
357 14.7 E357D