D346Y Summary

KCNH2 D346Y was found in 0 papers (see below) with a total of 1 carrier: 0 had LQT2. D346Y is present in 1 out of 250182 alleles in gnomAD (0.0004%). D346Y has been functionally characterized in 0 papers. 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.


D346Y 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.

D346Y 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
-11 0.698 -4.251 0.986 -3

D346Y 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
331 14.7 S331N S331T
332 14.2
333 13.7
334 13.2 P334L
335 12.6 Q335X
336 12
337 11.4 T337S T337X
338 10.7
339 10.1
340 9.3 F340L
341 8.5
342 7.6 D342A D342V D342X
343 6.6 L343fsX
344 5.4
345 3.8 G345S
347 3.8 P347S
348 5.4
349 6.6
350 7.6
351 8.5 S351L
352 9.3
353 10.1 T353S
354 10.7
355 11.4 D355G
356 12 R356C R356H
357 12.6 E357D
358 13.2
359 13.7 I359V
360 14.2
361 14.7