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NM_002693.3(POLG):c.3211C>T (p.Arg1071Cys) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 7, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000850154.1

Allele description [Variation Report for NM_002693.3(POLG):c.3211C>T (p.Arg1071Cys)]

NM_002693.3(POLG):c.3211C>T (p.Arg1071Cys)

Genes:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
POLGARF:POLG alternative reading frame [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.3(POLG):c.3211C>T (p.Arg1071Cys)
HGVS:
  • NC_000015.10:g.89318993G>A
  • NG_008218.2:g.20803C>T
  • NG_011736.1:g.80031G>A
  • NM_001126131.2:c.3211C>T
  • NM_002693.3:c.3211C>TMANE SELECT
  • NP_001119603.1:p.Arg1071Cys
  • NP_002684.1:p.Arg1071Cys
  • NP_002684.1:p.Arg1071Cys
  • LRG_765t1:c.3211C>T
  • LRG_500:g.80031G>A
  • LRG_765:g.20803C>T
  • LRG_765p1:p.Arg1071Cys
  • NC_000015.9:g.89862224G>A
  • NC_000015.9:g.89862224G>A
  • NM_002693.2:c.3211C>T
Protein change:
R1071C
Links:
dbSNP: rs762593265
NCBI 1000 Genomes Browser:
rs762593265
Molecular consequence:
  • NM_001126131.2:c.3211C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.3211C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1
Synonyms:
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL DOMINANT 1
Identifiers:
MONDO: MONDO:0024528; MedGen: C1834846; OMIM: 157640

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000992341Johns Hopkins Genomics, Johns Hopkins University
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 7, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations.

Chan SS, Copeland WC.

Biochim Biophys Acta. 2009 May;1787(5):312-9. doi: 10.1016/j.bbabio.2008.10.007. Epub 2008 Oct 29. Review.

PubMed [citation]
PMID:
19010300
PMCID:
PMC2742478

Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions.

Van Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C.

Nat Genet. 2001 Jul;28(3):211-2.

PubMed [citation]
PMID:
11431686
See all PubMed Citations (3)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV000992341.1

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

Description

This POLG variant (rs762593265) is rare (<0.1%) in large population datasets (gnomAD: 2/250916 total alleles; 0.0008%; no homozygotes). POLG c.3211C>T has not been reported in ClinVar nor the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be tolerated. The arginine residue at this position is poorly evolutionarily conserved across the species assessed and a cysteine is present at this position in multiple species. This variant is located within the polymerase domain of pol gamma, which is the location of nearly all variants associated with autosomal dominant PEO. The clinical significance of c.3211C>T is uncertain at this time.

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

Last Updated: May 19, 2024