NM_002693.2(POLG):c.3151G>C (p.Gly1051Arg) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Sep 19, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000188604.3

Allele description [Variation Report for NM_002693.2(POLG):c.3151G>C (p.Gly1051Arg)]

NM_002693.2(POLG):c.3151G>C (p.Gly1051Arg)

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.3151G>C (p.Gly1051Arg)
HGVS:
  • NC_000015.10:g.89319053C>G
  • NG_008218.2:g.20743G>C
  • NM_002693.2:c.3151G>C
  • NP_002684.1:p.Gly1051Arg
  • LRG_765t1:c.3151G>C
  • LRG_765:g.20743G>C
  • LRG_765p1:p.Gly1051Arg
  • NC_000015.9:g.89862284C>G
  • NG_008218.1:g.20743G>C
  • P54098:p.Gly1051Arg
  • p.G1051R
Protein change:
G1051R; GLY1051ARG
Links:
UniProtKB: P54098#VAR_023684; OMIM: 174763.0010; dbSNP: rs121918049
NCBI 1000 Genomes Browser:
rs121918049
Molecular consequence:
  • NM_002693.2:c.3151G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000242227GeneDxcriteria provided, single submitter
Likely pathogenic
(Sep 19, 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, SCV000242227.9

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

Description

The G1051R variant in the POLG gene been reported previously in a family with autosomal recessive progressive external ophthalmoplegia, sensorimotor polyneuropathy, ataxia and deafness who harbored a second pathogenic variant on the other allele (Mancuso et al., 2004). This variant was not observed in approximately 6500 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 G1051R variant is a non-conservative amino acid substitution, which occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function, with functional studies demonstrating that the G1051R variant results in increased mitochondrial DNA (mtDNA) instability and causes mtDNA defects (Baruffini et al., 2007). The G1051R variant is a strong candidate for a pathogenic variant, which may be related to the speech delay and anxiety reported in this individual. However, the possibility it may be a rare benign variant cannot be excluded.

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

Last Updated: Mar 30, 2019

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