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

Clinical significance:Uncertain significance (Last evaluated: Sep 30, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000726559.3

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]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000345498EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Dec 28, 2017)
germlineclinical testing

Citation Link,

SCV000885996ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Nov 10, 2017)
germlineclinical testing

Citation Link,

SCV000892143Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Uncertain significance
(Sep 30, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknown2not providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000345498.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV000885996.1

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

Description

The p.Tyr131His variant (rs562847013) has been reported as a polymorphism in an individual diagnosed with mitochondrial disease and as an unclassified variant in an individual whose features were suggestive of POLG deficiency; however, inheritance and specific clinical information were not reported for these cases (González-Vioque 2006 and Tang 2011). The p.Tyr131His variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.037% in the non-Finnish European population (identified in 34 out of 92,102 chromosomes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 206492). The tyrosine at codon 131 is weakly conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing). Therefore, based on the available information, the clinical significance of the p.Tyr131His variant cannot be determined with certainty.

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

From Praxis fuer Humangenetik Tuebingen, SCV000892143.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 7, 2019

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