NC_012920.1(MT-ATP6):m.9176T>G AND Mitochondrial complex 5 (ATP synthase) deficiency, mitochondrial type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2009
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:: RCV000754649.1

Allele description [Variation Report for NC_012920.1(MT-ATP6):m.9176T>G]

NC_012920.1(MT-ATP6):m.9176T>G

Gene:

MT-ATP6:mitochondrially encoded ATP synthase 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

NC_012920.1(MT-ATP6):m.9176T>G

Other names:

MTATP6, 9176T-G, LEU217ARG; L217R

HGVS:

NC_012920.1:m.9176T>G
m.9176T>G
p.Leu271Arg

Protein change:

LEU217ARG

Links:

Genetic Testing Registry (GTR): GTR000500595; OMIM: 516060.0011; dbSNP: rs199476135

NCBI 1000 Genomes Browser:

rs199476135

Condition(s)

Name:: Mitochondrial complex 5 (ATP synthase) deficiency, mitochondrial type 1
Synonyms:: Mitochondrial complex v (atp synthase) deficiency, mitochondrial type 1
Identifiers:: MONDO: MONDO:0027069; MedGen: C3275684; OMIM: 500015

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030509	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2009)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11245730, 19454486

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030509

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2009)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

The T9176G mtDNA mutation severely affects ATP production and results in Leigh syndrome.

Carrozzo R, Tessa A, Vázquez-Memije ME, Piemonte F, Patrono C, Malandrini A, Dionisi-Vici C, Vilarinho L, Villanova M, Schägger H, Federico A, Bertini E, Santorelli FM.

Neurology. 2001 Mar 13;56(5):687-90.

PubMed [citation]

PMID:: 11245730

Introducing the human Leigh syndrome mutation T9176G into Saccharomyces cerevisiae mitochondrial DNA leads to severe defects in the incorporation of Atp6p into the ATP synthase and in the mitochondrial morphology.

Kucharczyk R, Salin B, di Rago JP.

Hum Mol Genet. 2009 Aug 1;18(15):2889-98. doi: 10.1093/hmg/ddp226. Epub 2009 May 18.

PubMed [citation]

PMID:: 19454486

Details of each submission

From OMIM, SCV000030509.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a 10-year-old girl with severe neurodegenerative disorder consistent mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (MC5DM1; 500015), resulting in Leigh syndrome (see 256000), Carrozzo et al. (2001) identified a 9176T-G transversion in the MTATP6 gene. Her older sister had died of Leigh syndrome, and a maternal uncle had a spinocerebellar disorder. Biochemical studies revealed a reduced rate of ATP synthesis in patient skin fibroblast cultures.

Kucharczyk et al. (2009) created and analyzed the properties of a yeast strain bearing a mutation equivalent to the human 9176T-G mutation. Incorporation of mutant Atp6 within the ATP synthase was almost completely prevented in the mutant yeast. Based on previous characterization of human 9176T-G cells, it is likely that this mutation similarly affects the human ATP synthase instead of causing a block in the rotary mechanism of the enzyme as previously suggested. Mutant yeast exhibited important anomalies in mitochondrial morphology, indicating that the pathogenicity of 9176T-G may not be limited to a bioenergetic deficiency.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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