NM_004618.5(TOP3A):c.403C>T (p.Arg135Ter) AND Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 7, 2024
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:: RCV000678503.2

Allele description [Variation Report for NM_004618.5(TOP3A):c.403C>T (p.Arg135Ter)]

NM_004618.5(TOP3A):c.403C>T (p.Arg135Ter)

Gene:

TOP3A:DNA topoisomerase III alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_004618.5(TOP3A):c.403C>T (p.Arg135Ter)

HGVS:

NC_000017.11:g.18305208G>A
NM_001320759.2:c.118C>T
NM_004618.5:c.403C>TMANE SELECT
NP_001307688.1:p.Arg40Ter
NP_004609.1:p.Arg135Ter
NC_000017.10:g.18208522G>A
NM_004618.3:c.403C>T

Protein change:

R135*; ARG135TER

Links:

OMIM: 601243.0005; dbSNP: rs200944917

NCBI 1000 Genomes Browser:

rs200944917

Molecular consequence:

NM_001320759.2:c.118C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004618.5:c.403C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5
Synonyms:: PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL RECESSIVE 5
Identifiers:: MONDO: MONDO:0020845; MedGen: C4748184; OMIM: 618098

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000804570	OMIM	no assertion criteria provided	Pathogenic (Mar 7, 2024)	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

SCV000804570

OMIM

no assertion criteria provided

Pathogenic
(Mar 7, 2024)

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

Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA.

Nicholls TJ, Nadalutti CA, Motori E, Sommerville EW, Gorman GS, Basu S, Hoberg E, Turnbull DM, Chinnery PF, Larsson NG, Larsson E, Falkenberg M, Taylor RW, Griffith JD, Gustafsson CM.

Mol Cell. 2018 Jan 4;69(1):9-23.e6. doi: 10.1016/j.molcel.2017.11.033. Epub 2017 Dec 28.

PubMed [citation]

PMID:: 29290614
PMCID:: PMC5935120

Details of each submission

From OMIM, SCV000804570.2

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

Description

For discussion of the c.403C-T transition (c.403C-T, NM_004618.3) in the TOP3A gene, resulting in an arg135-to-ter (R135X) substitution, that was found in compound heterozygous state in a patient with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-5 (PEOB5; 618098) by Nicholls et al. (2018), see 601243.0004.

#	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: Mar 16, 2024

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