NM_002693.2(POLG):c.744G>C (p.Glu248Asp) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Apr 11, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000498616.1

Allele description [Variation Report for NM_002693.2(POLG):c.744G>C (p.Glu248Asp)]

NM_002693.2(POLG):c.744G>C (p.Glu248Asp)

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.744G>C (p.Glu248Asp)
HGVS:
  • NC_000015.10:g.89330192C>G
  • NG_008218.2:g.9604G>C
  • NM_002693.2:c.744G>C
  • NP_002684.1:p.Glu248Asp
  • LRG_765t1:c.744G>C
  • LRG_765:g.9604G>C
  • LRG_765p1:p.Glu248Asp
  • NC_000015.9:g.89873423C>G
Protein change:
E248D
Links:
dbSNP: rs753407311
NCBI 1000 Genomes Browser:
rs753407311
Molecular consequence:
  • NM_002693.2:c.744G>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
SCV000589456GeneDxcriteria provided, single submitter
Uncertain significance
(Apr 11, 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, SCV000589456.2

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

Description

The E248D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. 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. Missense variants in nearby residues (L244P, T251I) have been reported in the Human Gene Mutation Database in association with POLG-related disorders (Stenson et al., 2014). However, the E248D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved and n silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

Last Updated: Apr 17, 2019

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