NM_002693.2(POLG):c.264C>G (p.Phe88Leu) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000431950.2

Allele description [Variation Report for NM_002693.2(POLG):c.264C>G (p.Phe88Leu)]

NM_002693.2(POLG):c.264C>G (p.Phe88Leu)

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.264C>G (p.Phe88Leu)
HGVS:
  • NC_000015.10:g.89333491G>C
  • NG_008218.2:g.6305C>G
  • NM_002693.2:c.264C>G
  • NP_002684.1:p.Phe88Leu
  • LRG_765t1:c.264C>G
  • LRG_765:g.6305C>G
  • LRG_765p1:p.Phe88Leu
  • NC_000015.9:g.89876722G>C
Protein change:
F88L
Links:
dbSNP: rs144439703
NCBI 1000 Genomes Browser:
rs144439703
Molecular consequence:
  • NM_002693.2:c.264C>G - 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
SCV000520841GeneDxcriteria provided, single submitter
Likely pathogenic
(Aug 24, 2018)
germlineclinical testing

Citation Link,

SCV000802097Mayo Clinic Genetic Testing Laboratories,Mayo Clinicno assertion criteria providedUncertain significance
(Nov 1, 2017)
unknownclinical testing

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000520841.4

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

Description

A variant that is likely pathogenic has been identified in the POLG gene. The F88L variant has been reported previously in trans with a known pathogenic POLG variant in an adult referred for POLG testing but in whom no clinical information was provided (Tang et al., 2011). This variant was subsequently reported as an unclassified variant in a patient who did not have a second variant in POLG and in two patients with second variants found to have ataxia and other features (Tchikviladzé et al., 2015; Masingue et al., 2018). The F88L variant is observed in 7/34380 (0.02%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the F88L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

From Mayo Clinic Genetic Testing Laboratories,Mayo Clinic, SCV000802097.1

#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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