POLG Y831C - GET-Evidence

Curation:
Currentness:

POLG Y831C

(POLG Tyr831Cys)


Short summary

A rare polymorphism in POLG, probably benign. A small study of a nuclear family hypothesized it was causing Parkinson disease, but a later study found no significant difference in incidence between cases (1/140) and controls (5/127).

Variant evidence
Computational -1

Polyphen 2 predicts “probably damaging”

Functional -
Case/Control 1

Luoma et al’s observation of the variant in controls supports it not having any strong pathogenic effect.

See Luoma PT et al. 2007 (17846414).

Familial -

Mancuso et al’s family has a LOD of 1.2, but we evaluate the variant as benign based on Luoma et al’s later findings.

See Mancuso M et al. 2004 (15534189).

 
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

 

Allele frequency

  • C @ chr15:89865073: 0.8% (86/10758) in EVS
  • C @ chr15:87666076: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 0.8% (86/10758)

Publications
 

Mancuso M, Filosto M, Oh SJ, DiMauro S. A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism. Arch Neurol. 2004 Nov;61(11):1777-9. PubMed PMID: 15534189.

Reported segregating in a family with parkinsonian symptoms. The pedigree has a LOD of 1.2 for the variant segregating with the disorder. The variant was not seen in 130 healthy controls, but we cannot report case/control statistics because this is a report of a single case rather than a screen for variant incidence among many cases.

Luoma PT, Eerola J, Ahola S, Hakonen AH, Hellström O, Kivistö KT, Tienari PJ, Suomalainen A. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology. 2007 Sep 11;69(11):1152-9. PubMed PMID: 17846414.

In an examination of POLG variants in Parkinson cases and controls, this was seen in 1 of 140 cases and 5 of 127 controls. The authors conclude the variant is a benign polymorphism.

Genomes
 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr15:89865073

 

GS06985 - var-GS06985-1100-36-ASM
het C @ chr15:87666077

 

Other external references
 

    dbSNP
  • rs41549716
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the POLG gene
    Progressive External Ophthalmoplegia with Mitochondrial DNA Dele
    Alpers-Huttenlocher Syndrome
    POLG-Related Disorders
    POLG-Related Sensory Ataxic Neuropathy, Dysarthria, and Ophthalm
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/POLG
    PolyPhen-2
  • Score: 0.991 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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