F557L Summary

KCNH2 F557L was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F557L is not present in gnomAD. F557L 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 4 individuals unaffected with LQT2 and 6 individuals affected with LQT2.


F557L 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.

F557L 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)
19892732 2009 Xeno

F557L 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)
19892732 2009 Xeno 17.80

F557L 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
-3 0.878 -5.751 0.853 0

F557L has 64 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
419 13.6
422 13.6 A422T
423 13.6
549 13.7 V549M
550 11.3
551 11.4 F551L
552 10.6 L552S
553 8 L553V
554 5.7
555 7.4
556 5.7
558 4.7 A558E A558P A558V
559 7.5 L559F L559H
560 5.7 I560fsX I560M
561 6.7 A561P A561T A561V
562 10.4 H562P H562Q H562R
563 10.8 W563C W563G W563X
564 10.5 L564L
565 12.6
566 14.7 C566F C566G C566R C566S
611 14.9 Y611D
614 14.2 A614T A614V
615 10.6 L615F L615V
616 14.1 Y616S
617 13.6 F617L F617V
618 9.5 T618S
619 6.6
620 11.3 S620G S620I
621 11.2 S621N S621R
622 7 L622F
623 8.4 T623I
624 12.3 S624N S624R
624 14.7 S624N S624R
625 13.7 V625E
641 13.8 S641F S641P
642 10.6 I642Del I642V
643 12.2
644 11.7 V644F V644I
644 13.1 V644F V644I
645 9.8 M645I M645L M645R M645V
645 14.6 M645I M645L M645R M645V
646 15
646 7.1
647 11.6
647 10.7
648 11.1 G648A
648 9.3 G648A
649 8.2
649 12.1
650 11.9 L650X
650 10.2 L650X
651 7.1 M651K
651 14.5 M651K
652 8.4 Y652X
652 14.7 Y652X
653 11.2
653 12.9
654 10.8
655 7.1
656 7.5 F656L
657 12.5 G657S G657V
658 12.5
659 11
660 14.2 S660L