D323E Summary

KCNH2 D323E was found in 1 paper (see below) with a total of 1 carrier: 1 had LQT2. D323E is not present in gnomAD. D323E has been functionally characterized in 0 papers. 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.


D323E Reported Clinical Data

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

D323E 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 0.729 -2.149 0.896 1

D323E 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
308 14.7 M308I M308R M308T M308V
309 14.2 H309Q H309Y
310 13.7 P310L P310X
311 13.2 L311R
312 12.6 R312C R312Del R312H
313 12
314 11.4 G314S
315 10.7
316 10.1
317 9.3 N317S
318 8.5
319 7.6 T319T
320 6.6 S320L S320W S320X
321 5.4 D321Y
322 3.8
324 3.8 L324L
325 5.4 V325M
326 6.6 R326C R326fsX R326H
327 7.6 Y327H
328 8.5 R328C R328fsX R328H
329 9.3
330 10.1 I330V
331 10.7 S331N S331T
332 11.4
333 12
334 12.6 P334L
335 13.2 Q335X
336 13.7
337 14.2 T337S T337X
338 14.7