NM_021830.5(TWNK):c.1001G>A (p.Arg334Gln) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, digenic

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2003
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:: RCV000004886.6

Allele description [Variation Report for NM_021830.5(TWNK):c.1001G>A (p.Arg334Gln)]

NM_021830.5(TWNK):c.1001G>A (p.Arg334Gln)

Gene:

TWNK:twinkle mtDNA helicase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.31

Genomic location:

Preferred name:

NM_021830.5(TWNK):c.1001G>A (p.Arg334Gln)

HGVS:

NC_000010.11:g.100989211G>A
NG_011646.1:g.3305C>T
NG_012624.1:g.6676G>A
NM_001163812.2:c.1001G>A
NM_001163813.2:c.-119-433G>A
NM_001163814.2:c.-119-433G>A
NM_001368275.1:c.-57-495G>A
NM_021830.5:c.1001G>AMANE SELECT
NP_001157284.1:p.Arg334Gln
NP_068602.2:p.Arg334Gln
NC_000010.10:g.102748968G>A
NM_021830.4:c.1001G>A
NR_160738.1:n.1669G>A
NR_160740.1:n.1669G>A
NR_160741.1:n.1669G>A
NR_160742.1:n.1669G>A
Q96RR1:p.Arg334Gln

Protein change:

R334Q; ARG334GLN

Links:

UniProtKB: Q96RR1#VAR_023651; OMIM: 606075.0008; dbSNP: rs28937887

NCBI 1000 Genomes Browser:

rs28937887

Molecular consequence:

NM_001163813.2:c.-119-433G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001163814.2:c.-119-433G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001368275.1:c.-57-495G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001163812.2:c.1001G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.1001G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.1669G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.1669G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.1669G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.1669G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Progressive external ophthalmoplegia with mitochondrial DNA deletions, digenic
Identifiers:: MedGen: C1868097

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025062	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025062

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2003)

germline

literature only

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

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

Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle.

Van Goethem G, Löfgren A, Dermaut B, Ceuterick C, Martin JJ, Van Broeckhoven C.

Hum Mutat. 2003 Aug;22(2):175-6. No abstract available.

PubMed [citation]

PMID:: 12872260

Details of each submission

From OMIM, SCV000025062.4

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

Description

In a sporadic case of progressive external ophthalmoplegia (see 609286 and 157640), Van Goethem et al. (2003) identified heterozygosity for a 1031G-A transition in the C10ORF2 gene, resulting in an arg334-to-gln (R334Q) mutation, and heterozygosity for a gly884-to-ser mutation in the POLG gene (G884S; 174763.0006), indicating a digenic mode of inheritance. Clinical onset in the patient was at 52 years of age with blepharoptosis, depression, and levodopa-responsive Parkinson disease. Later she suffered from severe dysphagia leading to cachexia and necessitating enteric feeding. Sudden death, attributed to cardiac arrest, occurred at age 66 years.

#	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: Oct 20, 2024

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