NM_014874.4(MFN2):c.1126A>G (p.Met376Val) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 12, 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:: RCV002444815.9

Allele description [Variation Report for NM_014874.4(MFN2):c.1126A>G (p.Met376Val)]

NM_014874.4(MFN2):c.1126A>G (p.Met376Val)

Gene:

MFN2:mitofusin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_014874.4(MFN2):c.1126A>G (p.Met376Val)

HGVS:

NC_000001.11:g.12002069A>G
NG_007945.1:g.26889A>G
NM_001127660.2:c.1126A>G
NM_014874.4:c.1126A>GMANE SELECT
NP_001121132.1:p.Met376Val
NP_055689.1:p.Met376Val
NP_055689.1:p.Met376Val
LRG_255t1:c.1126A>G
LRG_255:g.26889A>G
LRG_255p1:p.Met376Val
NC_000001.10:g.12062126A>G
NM_014874.3:c.1126A>G

Protein change:

M376V

Links:

dbSNP: rs863224967

NCBI 1000 Genomes Browser:

rs863224967

Molecular consequence:

NM_001127660.2:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002753219	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Nov 12, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19889647, 22926664, 24473995, 28251916 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002753219

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Nov 12, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotypic spectrum of MFN2 mutations in the Spanish population.

Casasnovas C, Banchs I, Cassereau J, Gueguen N, Chevrollier A, Martínez-Matos JA, Bonneau D, Volpini V.

J Med Genet. 2010 Apr;47(4):249-56. doi: 10.1136/jmg.2009.072488. Epub 2009 Nov 3.

PubMed [citation]

PMID:: 19889647

Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion.

Vielhaber S, Debska-Vielhaber G, Peeva V, Schoeler S, Kudin AP, Minin I, Schreiber S, Dengler R, Kollewe K, Zuschratter W, Kornblum C, Zsurka G, Kunz WS.

Acta Neuropathol. 2013 Feb;125(2):245-56. doi: 10.1007/s00401-012-1036-y. Epub 2012 Aug 28.

PubMed [citation]

PMID:: 22926664

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002753219.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.M376V variant (also known as c.1126A>G), located in coding exon 9 of the MFN2 gene, results from an A to G substitution at nucleotide position 1126. The methionine at codon 376 is replaced by valine, an amino acid with highly similar properties. This variant has been identified de novo in an individual with MFN2-related neuropathy (Bansagi B et al. Neurology, 2017 Mar;88:1226-1234). This alteration has also been identified in multiple individuals with phenotype consistent with MFN2-related neuropathy (Casasnovas C et al. J. Med. Genet., 2010 Apr;47:249-56; Vielhaber S et al. Acta Neuropathol., 2013 Feb;125:245-56; Nightingale H et al. BMJ, 2014 Jan;348:g459). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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: Aug 25, 2024

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