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NM_001358921.2(COQ2):c.878T>C (p.Val293Ala) AND Multiple system atrophy

Germline classification:
risk factor (1 submission)
Last evaluated:
Jul 3, 2014
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000054429.8

Allele description [Variation Report for NM_001358921.2(COQ2):c.878T>C (p.Val293Ala)]

NM_001358921.2(COQ2):c.878T>C (p.Val293Ala)

Gene:
COQ2:coenzyme Q2, polyprenyltransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q21.23
Genomic location:
Preferred name:
NM_001358921.2(COQ2):c.878T>C (p.Val293Ala)
Other names:
V393A
HGVS:
  • NC_000004.12:g.83267659A>G
  • NG_015825.1:g.22256T>C
  • NM_001358921.2:c.878T>CMANE SELECT
  • NM_015697.9:c.1028T>C
  • NP_001345850.1:p.Val293Ala
  • NP_056512.5:p.Val343Ala
  • NC_000004.11:g.84188812A>G
Protein change:
V293A; VAL393ALA
Links:
OMIM: 609825.0007; dbSNP: rs397514727
NCBI 1000 Genomes Browser:
rs397514727
Molecular consequence:
  • NM_001358921.2:c.878T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015697.9:c.1028T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Multiple system atrophy (MSA)
Synonyms:
Shy-Drager syndrome; Multiple system atrophy (MSA) with orthostatic hypotension; Orthostatic hypotension, bladder and bowel incontinence, anhidrosis, iris atrophy, amyotrophy, ataxia, rigidity and tremor; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007803; MedGen: C0393571; Orphanet: 102

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000082906OMIM
no assertion criteria provided
risk factor
(Jul 3, 2014) 		germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in COQ2 in familial and sporadic multiple-system atrophy.

Multiple-System Atrophy Research Collaboration..

N Engl J Med. 2013 Jul 18;369(3):233-44. doi: 10.1056/NEJMoa1212115. Epub 2013 Jun 12. Erratum in: N Engl J Med. 2014 Jul 3;371(1):94.

PubMed [citation]
PMID:
23758206

Mutant COQ2 in multiple-system atrophy.

Jeon BS, Farrer MJ, Bortnick SF; Korean Canadian Alliance on Parkinson’s Disease and Related Disorders..

N Engl J Med. 2014 Jul 3;371(1):80. doi: 10.1056/NEJMc1311763. No abstract available.

PubMed [citation]
PMID:
24988567
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000082906.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

Jeon et al. (2014) noted that this mutation is a c.1178T-C transition in the COQ2 gene, resulting in a val393-to-ala (V393A) substitution, based on the NCBI reference sequence (NM_015697.7) and not a val343-to-ala substitution as originally published by The Multiple-System Atrophy Research Collaboration (2013).

The Multiple-System Atrophy Research Collaboration (2013) found that a val393-to-ala variant in the COQ2 gene was associated with multiple system atrophy-1 (146500) in Japanese patients. V393A was present in homozygous state with another pathogenic homozygous mutation (M128V; 609825.0006) in 2 Japanese sibs with the disorder. It was also found in compound heterozygosity with R387X (609825.0008) in 2 additional Japanese sibs from another family with the disorder. Among 363 Japanese patients with sporadic MSA1, homozygous V393A was found in 2 patients and none of 520 controls, and heterozygous V393A was found in 31 patients and 17 controls; 2 heterozygous carriers were compound heterozygous with another potentially pathogenic COQ2 variant. The allele frequency was 4.8% in Japanese patients and 1.6% in Japanese controls (odds ratio (OR) for MSA1 of 3.05, p = 1.5 x 10(-4)). Genotyping in a second series of 2,383 Japanese controls showed that the V393A variant had an allele frequency of 2.2%, yielding an OR of 2.23 (p = 6.0 x 10(-5)). Two patients with Alzheimer disease (AD; 104300) who were found to carry a homozygous V393A mutation did not show any signs of parkinsonism, cerebellar ataxia, or autonomic dysfunction. Otherwise, the V393A variant appeared to be specific for MSA. V393A was not found in 395 patients or 609 controls from European/North American cohorts. In vitro functional expression assays in yeast Coq2-null strains showed that the V393A variant could restore growth similar to wildtype, but showed somewhat decreased COQ2 activities in cell lines derived from patients with MSA.

Jeon et al. (2014) did not find an association between the V393A variant and multiple system atrophy among 299 Korean patients with the disorder and 365 controls (minor allele frequency 2.7% of cases versus 2.6% of controls).

Sharma et al. (2014) did not find the V393A variant in a large cohort of 788 European patients with MSA or 600 European controls.

Schottlaender and Houlden (2014) did not find the V393A variant in more than 300 European patients with MSA or 262 European controls.

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

Last Updated: Oct 28, 2023