U.S. flag

An official website of the United States government

NM_002437.5(MPV17):c.293C>T (p.Pro98Leu) AND MPV17-related disorder

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Apr 27, 2017
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:
RCV000312148.14

Allele description [Variation Report for NM_002437.5(MPV17):c.293C>T (p.Pro98Leu)]

NM_002437.5(MPV17):c.293C>T (p.Pro98Leu)

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.293C>T (p.Pro98Leu)
Other names:
p.P98L:CCG>CTG
HGVS:
  • NC_000002.12:g.27312576G>A
  • NG_008075.1:g.14989C>T
  • NG_033055.1:g.688C>T
  • NM_002437.5:c.293C>TMANE SELECT
  • NP_002428.1:p.Pro98Leu
  • NC_000002.11:g.27535443G>A
  • NM_002437.4:c.293C>T
  • P39210:p.Pro98Leu
Note:
NCBI staff reviewed the trace in Figure 3 of the paper by Blakely et al., 2012 (PubMed 22508010) to clarify the definition of this variant.
Protein change:
P98L; PRO98LEU
Links:
UniProtKB: P39210#VAR_076203; OMIM: 137960.0008; dbSNP: rs267607258
NCBI 1000 Genomes Browser:
rs267607258
Molecular consequence:
  • NM_002437.5:c.293C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
MPV17-related disorder
Synonyms:
MPV17-Related Disorders; MPV17-related condition
Identifiers:
MedGen: CN239328

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
SCV000429733Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Pathogenic
(Apr 27, 2017) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link,

SCV005363677PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Mar 28, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mitochondrial DNA depletion syndrome causing liver failure.

Bijarnia-Mahay S, Mohan N, Goyal D, Verma IC.

Indian Pediatr. 2014 Aug;51(8):666-8.

PubMed [citation]
PMID:
25129007

The Human Mitochondrial DNA Depletion Syndrome Gene MPV17 Encodes a Non-selective Channel That Modulates Membrane Potential.

Antonenkov VD, Isomursu A, Mennerich D, Vapola MH, Weiher H, Kietzmann T, Hiltunen JK.

J Biol Chem. 2015 May 29;290(22):13840-61. doi: 10.1074/jbc.M114.608083. Epub 2015 Apr 10.

PubMed [citation]
PMID:
25861990
PMCID:
PMC4447960
See all PubMed Citations (8)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000429733.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The MPV17 c.293C>T (p.Pro98Leu) variant has been reported in at least eight studies in which it is found in a total of ten individuals with mitochondrial DNA depletion-related syndromes, including four in a homozygous state (two of whom were siblings) and six in a compound heterozygous state (El-Hattab et al. 2010; Blakely et al. 2012; Uusimaa et al. 2014; Mendelsohn et al. 2014; Bijarnia-Mahay et al. 2014; Harvengt et al. 2014; Kim et al. 2016; Khoda et al. 2016). Mitochondrial DNA was shown to be decreased by 20% in hepatic tissue in one of the compound heterozygous individuals (Khoda et al. 2016). The variant has also been detected in a heterozygous state in four unaffected relatives of probands. Control data are unavailable for this variant which is reported at a frequency of 0.00006 in the European (non-Finnish) population of the Exome Aggregation Consortium. The MPV17 protein functions as a non-selective channel modulating the membrane potential to preserve mitochondrial homeostasis, and functional studies demonstrated that the p.Pro98Leu variant impacts the ability of the channel to close tightly (Antonenkov et al. 2015). Based on the evidence, the p.Pro98Leu variant is classified as pathogenic for MPV17-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

From PreventionGenetics, part of Exact Sciences, SCV005363677.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MPV17 c.293C>T variant is predicted to result in the amino acid substitution p.Pro98Leu. This variant has been reported in the homozygous and compound heterozygous states in individuals with mitochondrial DNA depletion syndrome (Blakely et al. 2012. PubMed ID: 22508010; Bijarnia-Mahay et al. 2014. PubMed ID: 25129007; Uusimaa et al. 2014. PubMed ID: 23714749; Kim et al. 2016. PubMed ID: 27536553; El-Hattab et al. 2010. PubMed ID: 20074988). This variant is reported in 0.016% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic.

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

Last Updated: Oct 26, 2024