F508L Summary

KCNH2 F508L was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F508L is not present in gnomAD. F508L 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.

F508L 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.

F508L 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
NA 0.836 -5.427 0.225 0

F508L has 28 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
425 14.2
429 14.8 A429P A429V
456 13.1 D456Y
457 12.6 L457P
459 14.9
460 10.9 D460fsX
461 14.7
463 14.9 F463L
464 13.7 I464X
502 12.4 M502I
503 10.3
504 10.5 A504V
505 9.5 A505V
506 6.1 I506V
507 4.5 P507L P507S
509 6.3 D509N
510 6.2
520 11.9
521 9.1
522 9.7 G522E
523 11.3
524 6.5
525 8 K525N
526 11.4
527 10.2
528 9.9 R528P R528W R528X
530 14.6
531 13.7 R531Del R531Q R531W