NM_002693.2(POLG):c.679C>T (p.Arg227Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 8, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000255169.2

Allele description [Variation Report for NM_002693.2(POLG):c.679C>T (p.Arg227Trp)]

NM_002693.2(POLG):c.679C>T (p.Arg227Trp)

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.679C>T (p.Arg227Trp)
HGVS:
  • NC_000015.10:g.89330257G>A
  • NG_008218.2:g.9539C>T
  • NM_002693.2:c.679C>T
  • NP_002684.1:p.Arg227Trp
  • LRG_765t1:c.679C>T
  • LRG_765:g.9539C>T
  • LRG_765p1:p.Arg227Trp
  • NC_000015.9:g.89873488G>A
  • NG_008218.1:g.9539C>T
  • P54098:p.Arg227Trp
Protein change:
R227W; ARG227TRP
Links:
UniProtKB: P54098#VAR_023663; OMIM: 174763.0021; dbSNP: rs121918056
NCBI 1000 Genomes Browser:
rs121918056
Molecular consequence:
  • NM_002693.2:c.679C>T - 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
SCV000322023GeneDxcriteria provided, single submitter
Pathogenic
(Oct 8, 2016)
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, SCV000322023.5

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

Description

The R227W missense variant in the POLG gene has been reported multiple times previously in individuals with POLG-related disorders who had a second POLG variant identified on the opposite allele (Agostino et al., 2003; Human DNA Polymerase Gamma Mutation Database). It was not observed in approximately 6,500 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 R227W 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, and this substitution occurs at a position that is conserved across species. Therefore, R227W is considered to be a pathogenic variant.

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

Last Updated: Mar 30, 2019

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