F656A Summary

KCNH2 F656A was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F656A is not present in gnomAD. F656A has been functionally characterized in 13 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 5 individuals unaffected with LQT2 and 5 individuals affected with LQT2.


F656A 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.

F656A 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)
12839862 2003 HEK293
17325511 2007 Xeno
18690032 2007 Xeno

F656A 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)
12839862 2003 HEK293
17325511 2007 Xeno -6.80 -66.00
18690032 2007 Xeno -10.90

F656A 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 NA NA NA NA

F656A has 63 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
547 14.8 A547T
549 12.3 V549M
550 9.7
551 13.5 F551L
552 12.4 L552S
553 7.7 L553V
554 7.5
555 12
556 10.5
557 7.5
558 12 A558E A558P A558V
559 14.5 L559F L559H
560 12.1 I560fsX I560M
561 13.9 A561P A561T A561V
619 12.1
620 14.6 S620G S620I
621 14.4 S621N S621R
622 10.3 L622F
622 13.9 L622F
623 9.6 T623I
623 14.5 T623I
624 13.3 S624N S624R
624 12.1 S624N S624R
625 14.7 V625E
644 14.4 V644F V644I
645 12.3 M645I M645L M645R M645V
646 9.7
647 11.4
647 13
648 10.1 G648A
648 9.4 G648A
649 11
649 6.2
650 6.9 L650X
650 10.7 L650X
651 10.8 M651K
651 7.6 M651K
652 5 Y652X
652 13 Y652X
652 9.9 Y652X
653 6.5
653 6.6
654 6.9
654 9.1
655 12.6
655 4.3
657 13.6 G657S G657V
657 11.7 G657S G657V
657 5.7 G657S G657V
658 7.2
658 13.9
659 5.4
659 13.7
660 11.1 S660L
660 7.1 S660L
661 10 A661V
661 14.7 A661V
662 10.5
663 10.8
663 13.3
664 13.6 Q664X
664 13.2 Q664X
665 14.8 R665Q