NM_002693.2(POLG):c.679C>T (p.Arg227Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 8, 2016)

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.679C>T (p.Arg227Trp)]

NM_002693.2(POLG):c.679C>T (p.Arg227Trp)

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.679C>T (p.Arg227Trp)
  • NC_000015.10:g.89330257G>A
  • NG_008218.2:g.9539C>T
  • NM_002693.2:c.679C>T
  • NP_002684.1:p.Arg227Trp
  • LRG_765t1:c.679C>T
  • LRG_765:g.9539C>T
  • LRG_765p1:p.Arg227Trp
  • NC_000015.9:g.89873488G>A
  • NG_008218.1:g.9539C>T
  • P54098:p.Arg227Trp
Protein change:
R227W; ARG227TRP
UniProtKB: P54098#VAR_023663; OMIM: 174763.0021; dbSNP: rs121918056
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_002693.2:c.679C>T - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000322023GeneDxcriteria provided, single submitter
(Oct 8, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000322023.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The R227W missense variant in the POLG gene has been reported multiple times previously in individuals with POLG-related disorders who had a second POLG variant identified on the opposite allele (Agostino et al., 2003; Human DNA Polymerase Gamma Mutation Database). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R227W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties, and this substitution occurs at a position that is conserved across species. Therefore, R227W is considered to be a pathogenic variant.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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