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NM_014874.4(MFN2):c.748C>T (p.Arg250Trp)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jul 4, 2021)
Last evaluated:
Sep 19, 2019
Accession:
VCV000543219.10
Variation ID:
543219
Description:
single nucleotide variant
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NM_014874.4(MFN2):c.748C>T (p.Arg250Trp)

Allele ID
515150
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p36.22
Genomic location
1: 11999027 (GRCh38) GRCh38 UCSC
1: 12059084 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.11:g.11999027C>T
NG_007945.1:g.23847C>T
NM_001127660.2:c.748C>T NP_001121132.1:p.Arg250Trp missense
... more HGVS
Protein change
R250W
Other names
-
Canonical SPDI
NC_000001.11:11999026:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
dbSNP: rs373107074
ClinGen: CA598916
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Sep 19, 2019 RCV000653915.3
Pathogenic 1 criteria provided, single submitter Jun 1, 2018 RCV001091327.2
Uncertain significance 2 no assertion criteria provided Aug 14, 2019 RCV000789065.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MFN2 No evidence available No evidence available GRCh38
GRCh37
775 822

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Sep 19, 2019)
criteria provided, single submitter
Method: clinical testing
Charcot-Marie-Tooth disease, type 2
Allele origin: germline
Invitae
Accession: SCV000775805.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with tryptophan at codon 250 of the MFN2 protein (p.Arg250Trp). The arginine residue is moderately conserved and there is a … (more)
Pathogenic
(Jun 01, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001247287.6
Submitted: (Jul 04, 2021)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: literature only
Charcot-Marie-Tooth disease
Allele origin: germline
Inherited Neuropathy Consortium
Accession: SCV000928414.1
Submitted: (Jul 10, 2019)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Aug 14, 2019)
no assertion criteria provided
Method: research
Charcot-Marie-Tooth disease
Allele origin: germline
Genesis Genome Database
Accession: SCV000999673.1
Submitted: (Aug 19, 2019)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Clinical and genetic diversities of Charcot-Marie-Tooth disease with MFN2 mutations in a large case study. Ando M Journal of the peripheral nervous system : JPNS 2017 PMID: 28660751
Clinical and genetic spectra of Charcot-Marie-Tooth disease in Chinese Han patients. Sun B Journal of the peripheral nervous system : JPNS 2017 PMID: 27862672
Clinical and allelic heterogeneity in a pediatric cohort of 11 patients carrying MFN2 mutation. Di Meglio C Brain & development 2016 PMID: 26686600
Mutational mechanisms in MFN2-related neuropathy: compound heterozygosity for recessive and semidominant mutations. Piscosquito G Journal of the peripheral nervous system : JPNS 2015 PMID: 26306937
MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Verhoeven K Brain : a journal of neurology 2006 PMID: 16714318

Text-mined citations for rs373107074...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 04, 2021