GRK5 Q41L - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

To be considered sufficiently evaluated a variant must have both "variant evidence" and "clinical importance" scores filled in.

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Curation:
Currentness:

GRK5 Q41L

(GRK5 Gln41Leu)


Short summary

 

Variant evidence
Computational 3

PolyPhen2: Benign, score 0.014
SIFT: Affect protein function 0.00
GVGD: GV 0.00; GD 112.44; Class C65
Variant Effect Predictor (Ensembl):
SIFT=tolerated(0.07);
PolyPhen=benign(0.014);
Condel=deleterious(0.839)
Mutation Tasting Prediction: Polymorphism, P value: 0.068269; protein features (might be) affected (aa 1-185 REGION N-terminal gets lost)

Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr10:121086097: 9.9% (1069/10758) in EVS
  • T @ chr10:121076086: 13.3% (17/128) in GET-Evidence
  • Frequency shown in summary reports: 9.9% (1069/10758)

Publications
 

Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, Diwan A, Martini JS, Sparks L, Parekh RR, Spertus JA, Koch WJ, Kardia SL, Dorn GW 2nd. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat Med. 2008 May;14(5):510-7. Epub 2008 Apr 20. PubMed PMID: 18425130; PubMed Central PMCID: PMC2596476.

 

Genomes
 

 

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr10:121086097

 

GS06985 - var-GS06985-1100-36-ASM
het T @ chr10:121076087

 

GS18501 - var-GS18501-1100-36-ASM
het T @ chr10:121076087

 

GS18502 - var-GS18502-1100-36-ASM
het T @ chr10:121076087

 

GS18504 - var-GS18504-1100-36-ASM
het T @ chr10:121076087

 

GS18505 - var-GS18505-1100-36-ASM
het T @ chr10:121076087

 

GS18508 - var-GS18508-1100-36-ASM
hom T @ chr10:121076087

 

GS18526 - var-GS18526-1100-36-ASM
het T @ chr10:121076087

 

GS19017 - var-GS19017-1100-36-ASM
het T @ chr10:121076087

 

GS19020 - var-GS19020-1100-36-ASM
het T @ chr10:121076087

 

GS19026 - var-GS19026-1100-36-ASM
het T @ chr10:121076087

 

GS19129 - var-GS19129-1100-36-ASM
het T @ chr10:121076087

 

GS19701 - var-GS19701-1100-36-ASM
het T @ chr10:121076087

 

GS19704 - var-GS19704-1100-36-ASM
het T @ chr10:121076087

 

GS19834 - var-GS19834-1100-36-ASM
het T @ chr10:121076087

 

Other external references
 

    dbSNP
  • rs17098707
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Heart Failure]
    This variant, present in approximately 40% of African Americans, is a nonsynonymous polymorphism of GRK5 that encodes a G protein-coupled receptor kinase in which Leucine is substituted for Glutamine at amino acid position 41. African American subjects with this variant had a longer time to death or cardiac transplantation than those without it, indicating a protective effect of GRK5-Leu 41. In transgenic mice, human GRK5-Leu41 is protective against cardiomyopathy induced by exposure to excessive catecholamine levels. In vitro experiments demonstrate that GRK5-Leu enhances desensitization of catecholamine-stimulated human beta-adrenergic receptors.
    www.ncbi.nlm.nih.gov/pubmed/18425130
    PolyPhen-2
  • Score: 0.016 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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