NM_002693.2(POLG):c.2636A>G (p.Gln879Arg) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Nov 20, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000188586.1

Allele description [Variation Report for NM_002693.2(POLG):c.2636A>G (p.Gln879Arg)]

NM_002693.2(POLG):c.2636A>G (p.Gln879Arg)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.2636A>G (p.Gln879Arg)
Other names:
p.Q879R:CAG>CGG
HGVS:
  • NC_000015.10:g.89321223T>C
  • NG_008218.2:g.18573A>G
  • NM_001126131.2:c.2636A>G
  • NM_002693.2:c.2636A>G
  • NP_001119603.1:p.Gln879Arg
  • NP_002684.1:p.Gln879Arg
  • LRG_765t1:c.2636A>G
  • LRG_765:g.18573A>G
  • LRG_765p1:p.Gln879Arg
  • NC_000015.9:g.89864454T>C
Protein change:
Q879R
Links:
dbSNP: rs368587966
NCBI 1000 Genomes Browser:
rs368587966
Molecular consequence:
  • NM_001126131.2:c.2636A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.2:c.2636A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000242208GeneDxcriteria provided, single submitter
Pathogenic
(Mar 5, 2014)
germlineclinical testing

Citation Link,

SCV000858276EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Nov 20, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000242208.9

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

Description

p.Gln879Arg (CAG>CGG): c.2636 A>G in exon 17 of the POLG gene (NM_002693.2). The Gln879Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 5,000 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 Gln879Arg mutation 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 in the polymerase domain of the protein and a different missense mutation at the same codon (Gln879His) was identified in a patient with hepatotoxicity and encephalopathy who had another disease-causing mutation on the other chromosome (Horvath et al., 2008; McFarland et al., 2008). Functional studies indicate that Gln879His moderately decreases the polymerase activity of the enzyme, confirming the functional importance of this position in the protein (Kasiviswanathan et al., 2009). The variant is found in INFANT-EPI,DEPLTN-MITOP,CHILD-EPI panel(s).

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

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000858276.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 12, 2021

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