NM_002437.5(MPV17):c.149G>A (p.Arg50Gln) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000712314.15

Allele description [Variation Report for NM_002437.5(MPV17):c.149G>A (p.Arg50Gln)]

NM_002437.5(MPV17):c.149G>A (p.Arg50Gln)

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.149G>A (p.Arg50Gln)

HGVS:

NC_000002.12:g.27313031C>T
NG_008075.1:g.14534G>A
NG_033055.1:g.233G>A
NM_002437.5:c.149G>AMANE SELECT
NP_002428.1:p.Arg50Gln
NC_000002.11:g.27535898C>T
NM_002437.4:c.149G>A
P39210:p.Arg50Gln

Protein change:

R50Q; ARG50GLN

Links:

UniProtKB: P39210#VAR_026217; OMIM: 137960.0001; dbSNP: rs121909721

NCBI 1000 Genomes Browser:

rs121909721

Molecular consequence:

NM_002437.5:c.149G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Paractinoplanes brasiliensis strain DSM 43805 Ga0197474_11, whole genome shotgun...
Paractinoplanes brasiliensis strain DSM 43805 Ga0197474_11, whole genome shotgun sequence
gi|1596174707|gb|SNWR01000001.1||gn :SNWR01|Ga0197474_11

Nucleotide
Model organism or animal sample from Canis latrans
Model organism or animal sample from Canis latrans

biosample
keratin, type I cuticular Ha3-I isoform X1 [Homo sapiens]
keratin, type I cuticular Ha3-I isoform X1 [Homo sapiens]
gi|2462498915|ref|XP_054189172.1|

Protein
Mycobacterium tuberculosis TB_RSA71
Mycobacterium tuberculosis TB_RSA71
TB-ARC - MRC SA

BioProject
3D domain-containing protein [Bacillus sp. PS11(2022)]
3D domain-containing protein [Bacillus sp. PS11(2022)]
gi|2711655302|ref|WP_339205287.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000842780	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Feb 9, 2022)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16909392, 20074988, 16582910, 18261905, 19012992, 32703289, 30833296, 30273399, 26467025
SCV000862602	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Pathogenic (Jul 24, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16582910, 16909392, 20074988 Citation Link,
SCV001202706	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16909392, 28209105, 16582910, 30833296, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000842780

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Feb 9, 2022)

unknown

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV000862602

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Pathogenic
(Jul 24, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001202706

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (5)
[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	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Lack of founder effect for an identical mtDNA depletion syndrome (MDS)-associated MPV17 mutation shared by Navajos and Italians.

Spinazzola A, Massa V, Hirano M, Zeviani M.

Neuromuscul Disord. 2008 Apr;18(4):315-8. doi: 10.1016/j.nmd.2007.12.007. Epub 2008 Feb 7.

PubMed [citation]

PMID:: 18261905

Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients.

Parini R, Furlan F, Notarangelo L, Spinazzola A, Uziel G, Strisciuglio P, Concolino D, Corbetta C, Nebbia G, Menni F, Rossi G, Maggioni M, Zeviani M.

J Hepatol. 2009 Jan;50(1):215-21. doi: 10.1016/j.jhep.2008.08.019. Epub 2008 Oct 31.

PubMed [citation]

PMID:: 19012992

See all PubMed Citations (11)

Details of each submission

From Athena Diagnostics, SCV000842780.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families. Computational tools predict that this variant is damaging.

#	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

From Eurofins Ntd Llc (ga), SCV000862602.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001202706.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 50 of the MPV17 protein (p.Arg50Gln). This variant is present in population databases (rs121909721, gnomAD 0.003%). This missense change has been observed in individuals with mitochondrial DNA depletion syndrome or Navajo neurohepatopathy (PMID: 16582910, 16909392, 28209105). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MPV17 function (PMID: 16582910, 30833296). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 13, 2024

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