NM_002693.2(POLG):c.391T>C (p.Tyr131His) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Sep 11, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000188542.8

Allele description [Variation Report for NM_002693.2(POLG):c.391T>C (p.Tyr131His)]

NM_002693.2(POLG):c.391T>C (p.Tyr131His)

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.391T>C (p.Tyr131His)
Other names:
p.Y131H:TAC>CAC
HGVS:
  • NC_000015.10:g.89333364A>G
  • NG_008218.2:g.6432T>C
  • NM_002693.2:c.391T>C
  • NP_002684.1:p.Tyr131His
  • LRG_765t1:c.391T>C
  • LRG_765:g.6432T>C
  • LRG_765p1:p.Tyr131His
  • NC_000015.9:g.89876595A>G
  • p.Y131H
Protein change:
Y131H
Links:
dbSNP: rs562847013
NCBI 1000 Genomes Browser:
rs562847013
Molecular consequence:
  • NM_002693.2:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000242160GeneDxcriteria provided, single submitter
Uncertain significance
(Sep 11, 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, SCV000242160.12

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

Description

A variant of uncertain significance has been identified in the POLG gene. The Y131H variant has been published as a benign variant in an individual; however, no clinical information was provided (Gonzalez-Vioque et al., 2006). The Y131H variant subsequently has been reported in an individual with a clinical presentation suggestive of POLG deficiency; however, additional clinical information was not provided and information regarding parental testing was not available (Tang et al., 2011). The authors concluded that Y131H is an unclassified variant (Tang et al., 2011). The Y131H variant is observed in 12/14298 (0.08%) alleles from individuals of European Non-Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y131H 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. However, this substitution occurs at a position that is not conserved. In 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: Mar 30, 2019

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