F640C Summary

KCNH2 F640C was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. F640C is not present in gnomAD. F640C 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 1 individuals unaffected with LQT2 and 9 individuals affected with LQT2.


F640C 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.

F640C 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)
19892744 2021 Xeno

F640C 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)
19892744 2021 Xeno -12.30

F640C 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
-13 0.901 -7.734 0.97 -3

F640C 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
560 12.2 I560fsX I560M
561 10.9 A561P A561T A561V
562 13.6 H562P H562Q H562R
563 12.6 W563C W563G W563X
564 6.7 L564L
565 9
566 10.7 C566F C566G C566R C566S
567 6.9 I567M I567T
568 6.1 W568C
569 12.1 Y569C Y569H Y569X
570 9.9
571 7.5 I571L I571V
572 11.4 G572C G572D G572R G572S
573 14
574 13.7 M574L M574V
575 12.9 E575K
584 13.7 G584C G584R G584S
585 10.8 W585C
586 14.4 L586M
612 12.1 V612A V612L
613 13.6 T613A T613K T613L T613M
613 13.9 T613A T613K T613L T613M
614 10.6 A614T A614V
615 13 L615F L615V
615 12.6 L615F L615V
616 10.3 Y616S
616 14.1 Y616S
617 8.2 F617L F617V
618 8.2 T618S
619 12.3
619 13
620 11.8 S620G S620I
620 13.2 S620G S620I
621 8.8 S621N S621R
622 10.7 L622F
623 14.2 T623I
623 14.4 T623I
624 14.7 S624N S624R
625 13.5 V625E
626 14.8 G626A G626S G626V
626 14.3 G626A G626S G626V
627 11.4 F627fsX F627L F627X
629 14.1 N629D N629I N629K N629S N629T
630 12.1 V630A V630I V630T
631 11.2 S631F
632 8.8 P632A P632S
633 12.3 N633D N633I N633S
634 10.3 T634A T634I T634P T634S
635 10.9 N635I
636 7.3
637 6.9 E637G E637K E637X
638 8.4 K638D K638Del K638E K638R
639 6.2 I639F I639N
641 4.8 S641F S641P
642 7.1 I642Del I642V
643 5.4
644 5.6 V644F V644I
645 8.6 M645I M645L M645R M645V
646 10.5
647 9.8
648 11.6 G648A
649 13.7
651 14.8 M651K