A547G Summary

KCNH2 A547G was found in 0 papers (see below) with a total of 0 carriers: 0 had LQT2. A547G is not present in gnomAD. A547G has been functionally characterized in 1 paper. 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.

A547G 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.

A547G 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)
24407947 2014 Xeno

A547G 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)
24407947 2014 Xeno 4.60

A547G 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
-2 0.905 -3.834 0.996 0

A547G has 37 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
412 11.5 W412X
415 14.1
539 13.8
540 14 D540fsX
541 14.3 R541C R541H
542 11.5
543 9.4 S543fsX
544 10.1 E544A E544fsX
545 6.7
546 3.3
548 3.6
549 5.5 V549M
550 5.3
551 7.6 F551L
552 9.1 L552S
553 10 L553V
554 11.1
555 12.2
556 14.2
650 13.5 L650X
654 14.8
655 14.5
656 14.8 F656L
658 12.8
659 10.4
660 13.1 S660L
661 12 A661V
662 8
663 9.5
664 13.5 Q664X
665 9.7 R665Q
666 7.4
667 10.6 Y667X
668 14 S668L
674 12.8 H674fsX H674Y
678 12.8
681 13.7 R681W