U.S. flag

An official website of the United States government

NM_021830.5(TWNK):c.1370C>T (p.Thr457Ile) AND Infantile onset spinocerebellar ataxia

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Dec 1, 2007
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:
RCV000004889.13

Allele description [Variation Report for NM_021830.5(TWNK):c.1370C>T (p.Thr457Ile)]

NM_021830.5(TWNK):c.1370C>T (p.Thr457Ile)

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.1370C>T (p.Thr457Ile)
HGVS:
  • NC_000010.11:g.100989770C>T
  • NG_011646.1:g.2746G>A
  • NG_012624.1:g.7235C>T
  • NM_001163812.2:c.1370C>T
  • NM_001163813.2:c.8C>T
  • NM_001163814.2:c.8C>T
  • NM_001368275.1:c.8C>T
  • NM_021830.5:c.1370C>TMANE SELECT
  • NP_001157284.1:p.Thr457Ile
  • NP_001157285.1:p.Thr3Ile
  • NP_001157286.1:p.Thr3Ile
  • NP_001355204.1:p.Thr3Ile
  • NP_068602.2:p.Thr457Ile
  • NC_000010.10:g.102749527C>T
  • NM_021830.3:c.1370C>T
  • NR_160738.1:n.2038C>T
  • NR_160739.1:n.198C>T
  • NR_160740.1:n.1976C>T
  • NR_160741.1:n.1976C>T
  • NR_160742.1:n.1976C>T
  • Q96RR1:p.Thr457Ile
Protein change:
T3I; THR457ILE
Links:
UniProtKB: Q96RR1#VAR_039045; OMIM: 606075.0011; dbSNP: rs80356544
NCBI 1000 Genomes Browser:
rs80356544
Molecular consequence:
  • NM_001163812.2:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001163813.2:c.8C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001163814.2:c.8C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368275.1:c.8C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021830.5:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_160738.1:n.2038C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160739.1:n.198C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160740.1:n.1976C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160741.1:n.1976C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160742.1:n.1976C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Infantile onset spinocerebellar ataxia (MTDPS7)
Synonyms:
Ophthalmoplegia, hypotonia, ataxia, hypacusis, and athetosis; Spinocerebellar ataxia 8 (formerly); SCA8 (formerly); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010060; MedGen: C1849096; Orphanet: 1186; OMIM: 271245

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000025065OMIM
no assertion criteria provided
Pathogenic
(Dec 1, 2007) 		germlineliterature only

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

SCV000041455GeneReviews
no classification provided
not providedgermlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion.

Sarzi E, Goffart S, Serre V, Chrétien D, Slama A, Munnich A, Spelbrink JN, Rötig A.

Ann Neurol. 2007 Dec;62(6):579-87.

PubMed [citation]
PMID:
17722119

Details of each submission

From OMIM, SCV000025065.3

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

Description

In 2 Algerian sibs and a first cousin with autosomal recessive mitochondrial DNA depletion syndrome-7 (MTDPS7; 271245), Sarzi et al. (2007) identified a homozygous 1370C-T transition in the C10ORF2 gene, resulting in a thr457-to-ile (T457I) substitution. All 3 patients were born of first-cousin parents and showed a severe hepatocerebral phenotype characterized by neonatal hypotonia, mild liver insufficiency, increased serum and CSF lactate, psychomotor retardation, seizures, and peripheral neuropathy. All 3 patients died by age 3 years. Mitochondrial DNA depletion was severe in 2 patients examined, with mtDNA levels in liver of 8% and 5% of normal, respectively. Molecular modeling predicted that the mutation is located in the interface between 2 monomers of the hexameric enzyme. In vitro functional expression studies showed that the T457I mutant protein had a more than 50% reduction in helicase activity. Family members who were presumed obligate carriers were unaffected.

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

From GeneReviews, SCV000041455.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024