NM_002693.2(POLG):c.2209G>C (p.Gly737Arg) AND Maternally-inherited progressive external ophthalmoplegia

Clinical significance:Likely pathogenic (Last evaluated: Mar 21, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000190616.2

Allele description [Variation Report for NM_002693.2(POLG):c.2209G>C (p.Gly737Arg)]

NM_002693.2(POLG):c.2209G>C (p.Gly737Arg)

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.2209G>C (p.Gly737Arg)
Other names:
p.G737R:GGA>CGA
HGVS:
  • NC_000015.10:g.89323460C>G
  • NG_008218.2:g.16336G>C
  • NM_002693.2:c.2209G>C
  • NP_002684.1:p.Gly737Arg
  • LRG_765t1:c.2209G>C
  • LRG_765:g.16336G>C
  • LRG_765p1:p.Gly737Arg
  • NC_000015.9:g.89866691C>G
  • NG_008218.1:g.16336G>C
  • P54098:p.Gly737Arg
Protein change:
G737R; GLY737ARG
Links:
UniProtKB: P54098#VAR_058885; OMIM: 174763.0019; dbSNP: rs121918054
NCBI 1000 Genomes Browser:
rs121918054
Molecular consequence:
  • NM_002693.2:c.2209G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Name:
Maternally-inherited progressive external ophthalmoplegia
Identifiers:
MedGen: CN924917; Orphanet: 663

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000245652Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Mar 21, 2017)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided44not providednot providednot providedclinical testing

Citations

PubMed

Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene.

Horvath R, Hudson G, Ferrari G, Fütterer N, Ahola S, Lamantea E, Prokisch H, Lochmüller H, McFarland R, Ramesh V, Klopstock T, Freisinger P, Salvi F, Mayr JA, Santer R, Tesarova M, Zeman J, Udd B, Taylor RW, Turnbull D, Hanna M, Fialho D, et al.

Brain. 2006 Jul;129(Pt 7):1674-84. Epub 2006 Apr 18.

PubMed [citation]
PMID:
16621917

Mitochondrial DNA depletion in progressive external ophthalmoplegia caused by POLG1 mutations.

Tzoulis C, Papingji M, Fiskestrand T, Røste LS, Bindoff LA.

Acta Neurol Scand Suppl. 2009;(189):38-41. doi: 10.1111/j.1600-0404.2009.01212.x.

PubMed [citation]
PMID:
19566497
See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000245652.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (7)

Description

The p.Gly737Arg (NM_002693.2 c.2209G>C) variant in POLG has been reported in 10 compound heterozygous individuals presenting with POLG-related mitochondrial DNA (mtDNA) depletion syndromes (Horvath 2006, Davidzon 2006, Wong 2008, Harrower 2008, Tzoulis 2009, Tang 2011). This variant has been identified in 0.1% (67/66514) of European chromosomes in ExAC though this frequency in consistent with a recessive carrier frequency. In summary, although additional studies are required to fully establish its clinical significance, the p. Gly737Arg variant is likely pathogenic for POLG-related mitochondrial DNA (mtDNA) depletion syndromes in an autosomal recessive manner based upon biallelic case observations and consistent allele frequency.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided4not provided4not provided

Last Updated: Apr 17, 2019

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