NM_002693.2(POLG):c.2209G>C (p.Gly737Arg) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jul 13, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000188568.6

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:
17

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000225831EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Jul 13, 2018)
germlineclinical testing

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

Citation Link,

SCV000242188GeneDxcriteria provided, single submitter
Pathogenic
(Jun 29, 2018)
germlineclinical testing

Citation Link,

SCV000280606Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinicscriteria provided, single submitter
Pathogenic
(Jan 11, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000614710Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Jan 31, 2017)
germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

SCV000802087Mayo Clinic Genetic Testing Laboratories,Mayo Clinicno assertion criteria providedUncertain significance
(Feb 26, 2016)
unknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown17not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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

Horvath R, Hudson G, Ferrari G, F├╝tterer N, Ahola S, Lamantea E, Prokisch H, Lochm├╝ller 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
See all PubMed Citations (16)

Details of each submission

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000225831.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided17not providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided17not providednot providednot provided

From GeneDx, SCV000242188.11

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

Description

The G737R pathogenic variant in the POLG gene has been reported in the presence of a second POLG variant in association with diverse clinical presentations of autosomal recessive POLG-related disorders that lead to early-onset parkinsonism, progressive external opthalmoplegia, sensory peripheral neuropathy, seizures, ataxia, hearing loss, myocerebrohepatopathy, and Charcot-Marie-Tooth disease (Davidzon et al., 2006; Horvath et al., 2006; Wong et al., 2008; Tzoulis et al., 2009; Tang et al., 2011; Rempe et al., 2016). While not seen in the homozygous state, the G737R variant is observed in 162/126,642 (0.1%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The G737R variant 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret G737R as a pathogenic variant.

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

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000280606.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot provided0.00157not providednot provided

From Athena Diagnostics Inc, SCV000614710.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Mayo Clinic Genetic Testing Laboratories,Mayo Clinic, SCV000802087.1

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

Last Updated: Apr 17, 2019

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