PKP2 L366P - GET-Evidence

Curation:
Currentness:

PKP2 L366P

(PKP2 Leu366Pro)


Short summary

This variant is a benign polymorphism.

Variant evidence
Computational 1

Variant Effect Predictor (Ensembl):
SIFT=tolerated(0.31);
PolyPhen=benign(0);
Condel=deleterious(0.692)
Mutation Tasting Prediction: Polymorphism, P value: 0.999996; protein features (might be) affected (aa 341-383 REPEAT ARM 1 gets lost)
PolyPhen2: Benign, score 0.000
SIFT: Tolerated 1.00
GVGD: GV 155.34; GD 0.00; Class C0
Multi-alignment with panda, Rhesus monkey, cattle, horse, rabbit, gibbon, and orangutan.

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

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

This variant was reported as a benign polymorphism by Christensen et al.

Allele frequency

  • G @ chr12:33021934: 22.1% (2380/10758) in EVS
  • G @ chr12:32913200: 13.7% (17/124) in GET-Evidence
  • Frequency shown in summary reports: 22.1% (2380/10758)

Publications
 

Christensen AH, Benn M, Tybjaerg-Hansen A, Haunso S, Svendsen JH. Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients--disease-causing or innocent bystanders? Cardiology. 2010;115(2):148-54. Epub 2009 Dec 3. PubMed PMID: 19955750.

This variant was reported as a benign polymorphism. The authors reported seeing the variant in patients (1097T>C; 9 heterozygous, 5 homozygous patients) without reporting the frequency in controls.

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het G @ chr12:33021934

 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het G @ chr12:33021934

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het G @ chr12:33021934

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het G @ chr12:33021934

 

hu2DBF2D - CGI sample GS01173-DNA_G02 from PGP sample 67180598
het G @ chr12:33021934

 

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
hom G @ chr12:33021934

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
hom G @ chr12:33021934

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het G @ chr12:33021934

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
hom G @ chr12:33021934

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het G @ chr12:33021934

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
hom G @ chr12:33021934

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het G @ chr12:33021934

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het G @ chr12:33021934

 

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het G @ chr12:33021934

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr12:33021934

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het G @ chr12:33021934

 

GS18502 - var-GS18502-1100-36-ASM
hom G @ chr12:32913201

 

GS18555 - var-GS18555-1100-36-ASM
het G @ chr12:32913201

 

GS19129 - var-GS19129-1100-36-ASM
het G @ chr12:32913201

 

GS19238 - var-GS19238-1100-36-ASM
het G @ chr12:32913201

 

GS19239 - var-GS19239-1100-36-ASM
het G @ chr12:32913201

 

GS19240 - var-GS19240-1100-36-ASM
het G @ chr12:32913201

 

GS19649 - var-GS19649-1100-36-ASM
hom G @ chr12:32913201

 

GS19701 - var-GS19701-1100-36-ASM
het G @ chr12:32913201

 

GS19704 - var-GS19704-1100-36-ASM
het G @ chr12:32913201

 

GS20502 - var-GS20502-1100-36-ASM
het G @ chr12:32913201

 

GS21767 - var-GS21767-1100-36-ASM
het G @ chr12:32913201

 

NA12878

 

Other external references
 

    dbSNP
  • rs1046116
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the PKP2 gene
    Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autos
    Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PKP2

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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