NM_015560.2(OPA1):c.869G>A (p.Arg290Gln) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 17, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000790668.6

Allele description [Variation Report for NM_015560.2(OPA1):c.869G>A (p.Arg290Gln)]

NM_015560.2(OPA1):c.869G>A (p.Arg290Gln)

Gene:
OPA1:OPA1 mitochondrial dynamin like GTPase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q29
Genomic location:
Preferred name:
NM_015560.2(OPA1):c.869G>A (p.Arg290Gln)
Other names:
R290Q
HGVS:
  • NC_000003.12:g.193637280G>A
  • NG_011605.1:g.49137G>A
  • NM_001354663.2:c.500G>A
  • NM_001354664.2:c.497G>A
  • NM_015560.2:c.869G>A
  • NM_130831.3:c.761G>A
  • NM_130832.3:c.815G>A
  • NM_130833.2:c.872G>A
  • NM_130834.3:c.923G>A
  • NM_130835.2:c.926G>A
  • NM_130836.3:c.980G>A
  • NM_130837.2:c.1034G>A
  • NP_001341592.1:p.Arg167Gln
  • NP_001341593.1:p.Arg166Gln
  • NP_056375.2:p.Arg290Gln
  • NP_056375.2:p.Arg290Gln
  • NP_570844.1:p.Arg254Gln
  • NP_570845.1:p.Arg272Gln
  • NP_570846.1:p.Arg291Gln
  • NP_570847.2:p.Arg308Gln
  • NP_570848.1:p.Arg309Gln
  • NP_570849.2:p.Arg327Gln
  • NP_570850.2:p.Arg345Gln
  • LRG_337t1:c.869G>A
  • LRG_337t2:c.1034G>A
  • LRG_337:g.49137G>A
  • LRG_337p1:p.Arg290Gln
  • LRG_337p2:p.Arg345Gln
  • NC_000003.11:g.193355069G>A
  • O60313:p.Arg290Gln
Protein change:
R166Q; ARG290GLN
Links:
NCBI 1000 Genomes Browser:
rs121908375
Molecular consequence:
  • NM_001354663.2:c.500G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354664.2:c.497G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015560.2:c.869G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130831.3:c.761G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130832.3:c.815G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130833.2:c.872G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130834.3:c.923G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130835.2:c.926G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130836.3:c.980G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130837.2:c.1034G>A - 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
SCV000232749EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Jan 6, 2016)
germlineclinical testing

Citation Link,

SCV001762175Institute of Medical Genetics and Applied Genomics, University Hospital Tübingencriteria provided, single submitter
Likely pathogenic
(Jun 17, 2021)
germlineclinical testing

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

SCV001787297GeneDxcriteria provided, single submitter
Pathogenic
(Sep 29, 2020)
germlineclinical testing

Citation Link,

SCV001880554Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Feb 19, 2021)
unknownclinical testing

PubMed (14)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot provided1not providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Mutation spectrum and splicing variants in the OPA1 gene.

Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L, Lenaers G, Belenguer P, Hamel CP.

Hum Genet. 2001 Dec;109(6):584-91. Epub 2001 Oct 30.

PubMed [citation]
PMID:
11810270
See all PubMed Citations (15)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000232749.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001762175.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

From GeneDx, SCV001787297.1

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

Description

Functional studies support a deleterious effect on mitochondrial morphology and cellular reactive oxygen species level (Zhang et al., 2016; Olichon et al., 2007); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 33300680, 27858935, 30293569, 22779427, 21745197, 23916084, 25564500, 11017080, 17167772, 26867657, 32025183)

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

From Athena Diagnostics Inc, SCV001880554.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. This variant segregates with disease in multiple families. Assessment of experimental evidence suggests this variant results in abnormal protein function. A study in mouse embryonic fibroblasts showed this variant caused significant decrease of mtDNA content and completely fragmented the mitochondrial network (PMID: 30293569). The variant is located in a region that is considered important for protein function and/or structure.

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

Last Updated: Oct 16, 2021

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