NM_002693.2(POLG):c.3323A>T (p.Tyr1108Phe) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jan 18, 2017)

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.3323A>T (p.Tyr1108Phe)]

NM_002693.2(POLG):c.3323A>T (p.Tyr1108Phe)

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.3323A>T (p.Tyr1108Phe)
Other names:
  • NC_000015.10:g.89318700T>A
  • NG_008218.2:g.21096A>T
  • NM_002693.2:c.3323A>T
  • NP_002684.1:p.Tyr1108Phe
  • LRG_765t1:c.3323A>T
  • LRG_765:g.21096A>T
  • LRG_765p1:p.Tyr1108Phe
  • NC_000015.9:g.89861931T>A
Protein change:
dbSNP: rs765949668
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_002693.2:c.3323A>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)
SCV000242138GeneDxcriteria provided, single submitter
Uncertain significance
(Jan 18, 2017)
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, SCV000242138.12

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


A variant of uncertain significance has been identified in the POLG gene. The Y1108F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Y1108F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y1108F 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. This substitution occurs at a position that is conserved across species. Multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with POLG-related (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

Last Updated: Apr 17, 2019

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