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NM_002693.3(POLG):c.2542G>A (p.Gly848Ser) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 24, 2009
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000014449.27

Allele description [Variation Report for NM_002693.3(POLG):c.2542G>A (p.Gly848Ser)]

NM_002693.3(POLG):c.2542G>A (p.Gly848Ser)

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.2542G>A (p.Gly848Ser)
Other names:
p.G848S:GGC>AGC; NM_001126131.1(POLG):c.2542G>A(p.Gly848Ser); NM_002693.2(POLG):c.2542G>A(p.Gly848Ser)
HGVS:
  • NC_000015.10:g.89321792C>T
  • NG_008218.2:g.18004G>A
  • NM_001126131.2:c.2542G>A
  • NM_002693.3:c.2542G>AMANE SELECT
  • NP_001119603.1:p.Gly848Ser
  • NP_002684.1:p.Gly848Ser
  • NP_002684.1:p.Gly848Ser
  • LRG_765t1:c.2542G>A
  • LRG_765:g.18004G>A
  • LRG_765p1:p.Gly848Ser
  • NC_000015.9:g.89865023C>T
  • NM_001126131.1:c.2542G>A
  • NM_002693.2:c.2542G>A
  • P54098:p.Gly848Ser
Protein change:
G848S; GLY848SER
Links:
UniProtKB: P54098#VAR_023675; OMIM: 174763.0006; dbSNP: rs113994098
NCBI 1000 Genomes Browser:
rs113994098
Molecular consequence:
  • NM_001126131.2:c.2542G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.2542G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 (PEOB1)
Synonyms:
Cerebellar ataxia infantile with progressive external ophthalmoplegia; Progressive external ophthalmoplegia, autosomal recessive 1
Identifiers:
MONDO: MONDO:0009783; MedGen: C4225153; Orphanet: 254886; OMIM: 258450

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034699OMIM
no assertion criteria provided
Pathogenic
(Mar 24, 2009) 		germlineliterature only

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia.

Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M.

Ann Neurol. 2002 Aug;52(2):211-9.

PubMed [citation]
PMID:
12210792

Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle.

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

Hum Mutat. 2003 Aug;22(2):175-6. No abstract available.

PubMed [citation]
PMID:
12872260
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000034699.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (6)

Description

In a patient with autosomal recessive PEO (PEOB1; 258450), Lamantea et al. (2002) identified compound heterozygosity for 2 mutations in the POLG gene: gly848-to-ser (G848S) and thr251-to-ile (T251I; 174763.0007).

In a patient with PEO, Van Goethem et al. (2003) identified a heterozygous G848S mutation in the POLG gene and a heterozygous arg334-to-gln mutation in the C10ORF2 gene (R334Q; 606075.0008), indicating a digenic mode of inheritance.

In 4 children with mitochondrial DNA depletion syndrome-4A (MTDPS4A; 203700), manifest as Alpers syndrome, Davidzon et al. (2005) identified compound heterozygosity for 2 mutations in the POLG gene: G848S and W748S (174763.0013). All patients died in childhood. Davidzon et al. (2005) noted that the G848S mutation occurs within the polymerase motif C of the enzyme.

Nguyen et al. (2005) reported 2 unrelated patients with mtDNA depletion syndrome-4A, manifest as Alpers syndrome. One was compound heterozygous for G848S and A467T (174763.0002), and the other was compound heterozygous for G848S and W748S.

Hakonen et al. (2007) presented evidence that the G848S disease chromosome originated from a common founder, possibly of European origin.

In an infant with mtDNA depletion syndrome-4B (MTDPS4B; 613662), manifest as severe hypotonia and gastrointestinal dysmotility (MNGIE), Giordano et al. (2009) identified compound heterozygosity for 2 mutations in the POLG gene: G848S and a 697C-T transition, resulting in an arg227-to-trp (R227W; 174763.0021) substitution. Other features included hearing loss and clubfoot. Brain MRI showed enlarged ventricles, but leukoencephalopathy was not noted. There was no liver damage aside from that resulting from parenteral nutrition. Analysis of the bowel showed that mtDNA depletion was mainly confined to the external layer of the muscularis propria.

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

Last Updated: May 7, 2024