NM_002437.5(MPV17):c.359G>A (p.Trp120Ter) AND Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000017547.32

Allele description [Variation Report for NM_002437.5(MPV17):c.359G>A (p.Trp120Ter)]

NM_002437.5(MPV17):c.359G>A (p.Trp120Ter)

Gene:

MPV17:mitochondrial inner membrane protein MPV17 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_002437.5(MPV17):c.359G>A (p.Trp120Ter)

HGVS:

NC_000002.12:g.27312510C>T
NG_008075.1:g.15055G>A
NG_033055.1:g.754G>A
NM_002437.5:c.359G>AMANE SELECT
NP_002428.1:p.Trp120Ter
NC_000002.11:g.27535377C>T

Protein change:

W120*; TRP120TER

Links:

OMIM: 137960.0005; dbSNP: rs121909724

NCBI 1000 Genomes Browser:

rs121909724

Molecular consequence:

NM_002437.5:c.359G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
Synonyms:: Navajo neurohepatopathy; Navajo neuropathy; Mitochondrial DNA depletion syndrome type 6
Identifiers:: MONDO: MONDO:0009747; MedGen: C1850406; Orphanet: 255229; OMIM: 256810

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037819	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000998877	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 13, 2019)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 18695062, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000037819

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2008)

germline

literature only

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

SCV000998877

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 13, 2019)

unknown

curation

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.

Spinazzola A, Santer R, Akman OH, Tsiakas K, Schaefer H, Ding X, Karadimas CL, Shanske S, Ganesh J, Di Mauro S, Zeviani M.

Arch Neurol. 2008 Aug;65(8):1108-13. doi: 10.1001/archneur.65.8.1108.

PubMed [citation]

PMID:: 18695062

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000037819.3

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

Description

In 2 sisters, born of consanguineous Iraqi parents, with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2008) identified a homozygous 359G-A transition in exon 5 of the MPV17 gene, resulting in a trp120-to-ter (W120X) substitution. Both died from rapidly progressive liver failure at ages 11 and 5 months, respectively.

#	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

From SIB Swiss Institute of Bioinformatics, SCV000998877.1

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

Description

This variant is interpreted as a Likely pathogenic for Mitochondrial DNA depletion syndrome 6, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PVS1-strong, PP1, PM3-supporting.

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

Last Updated: Sep 29, 2024

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