NM_002693.2(POLG):c.3139C>T (p.Arg1047Trp) AND Seizures

Clinical significance:Uncertain significance (Last evaluated: Nov 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_002693.2(POLG):c.3139C>T (p.Arg1047Trp)]

NM_002693.2(POLG):c.3139C>T (p.Arg1047Trp)

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_002693.2(POLG):c.3139C>T (p.Arg1047Trp)
Other names:
  • NC_000015.10:g.89319065G>A
  • NG_008218.2:g.20731C>T
  • NG_011736.1:g.80103G>A
  • NM_001126131.2:c.3139C>T
  • NM_002693.2:c.3139C>T
  • NP_001119603.1:p.Arg1047Trp
  • NP_002684.1:p.Arg1047Trp
  • LRG_765t1:c.3139C>T
  • LRG_500:g.80103G>A
  • LRG_765:g.20731C>T
  • LRG_765p1:p.Arg1047Trp
  • NC_000015.9:g.89862296G>A
  • p.Arg1047Trp
Protein change:
dbSNP: rs181860632
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001126131.2:c.3139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.2:c.3139C>T - missense variant - [Sequence Ontology: SO:0001583]


MedGen: C0036572; Human Phenotype Ontology: HP:0001250

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000851544Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Nov 24, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



Juvenile Alpers disease.

Wiltshire E, Davidzon G, DiMauro S, Akman HO, Sadleir L, Haas L, Zuccollo J, McEwen A, Thorburn DR.

Arch Neurol. 2008 Jan;65(1):121-4. doi: 10.1001/archneurol.2007.14.

PubMed [citation]

Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children.

Stewart JD, Tennant S, Powell H, Pyle A, Blakely EL, He L, Hudson G, Roberts M, du Plessis D, Gow D, Mewasingh LD, Hanna MG, Omer S, Morris AA, Roxburgh R, Livingston JH, McFarland R, Turnbull DM, Chinnery PF, Taylor RW.

J Med Genet. 2009 Mar;46(3):209-14. doi: 10.1136/jmg.2008.058180.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000851544.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)


The p.R1047W variant (also known as c.3139C>T), located in coding exon 19 of the POLG gene, results from a C to T substitution at nucleotide position 3139. The arginine at codon 1047 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was first reported in conjunction with a missense alteration (phase not specified) in an individual with suspected juvenile Alpers disease (occipital seizures, peripheral neuropathy, migraines, neuronal loss and gliosis predominantly in occipital lobe, mitochondrial DNA deletions in liver) and was absent among over 200 control alleles (Wiltshire E et al. Arch. Neurol., 2008 Jan;65:121-4). In another study, this variant was reported in conjunction with a missense alteration (phase not specified) in an individual with progressive external ophthalmoplegia (PEO), ataxia, and two affected siblings with spinocerebellar ataxia (SCA)-like phenotype (Stewart JD et al. J. Med. Genet., 2009 Mar;46:209-14; Lax NZ et al. Brain, 2012 Jan;135:62-71). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Jun 2, 2021

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