NM_002693.2(POLG):c.678G>C (p.Gln226His) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Sep 12, 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:
RCV000710188.3

Allele description [Variation Report for NM_002693.2(POLG):c.678G>C (p.Gln226His)]

NM_002693.2(POLG):c.678G>C (p.Gln226His)

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.678G>C (p.Gln226His)
Other names:
p.Q226H:CAG>CAC
HGVS:
  • NC_000015.10:g.89330258C>G
  • NG_008218.2:g.9538G>C
  • NM_002693.2:c.678G>C
  • NP_002684.1:p.Gln226His
  • LRG_765t1:c.678G>C
  • LRG_765:g.9538G>C
  • LRG_765p1:p.Gln226His
  • NC_000015.9:g.89873489C>G
Protein change:
Q226H
Links:
dbSNP: rs147282197
NCBI 1000 Genomes Browser:
rs147282197
Molecular consequence:
  • NM_002693.2:c.678G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000242262GeneDxcriteria provided, single submitter
Uncertain significance
(Sep 12, 2018)
germlineclinical testing

Citation Link,

SCV000614733Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(May 24, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000709292EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Jun 14, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown4not providednot providednot providednot providedclinical testing

Citations

PubMed

Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma.

Gasparre G, Hervouet E, de Laplanche E, Demont J, Pennisi LF, Colombel M, M├Ęge-Lechevallier F, Scoazec JY, Bonora E, Smeets R, Smeitink J, Lazar V, Lespinasse J, Giraud S, Godinot C, Romeo G, Simonnet H.

Hum Mol Genet. 2008 Apr 1;17(7):986-95. Epub 2007 Dec 21.

PubMed [citation]
PMID:
18156159

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000242262.12

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

Description

The Q226H variant has been reported previously 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 Q226H variant is observed in 94/124870 (0.1%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The Q226H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter 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

From Athena Diagnostics Inc, SCV000614733.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000709292.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided4not providednot providednot provided

Last Updated: Apr 17, 2019

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