NM_014874.4(MFN2):c.827A>G (p.Gln276Arg) AND Inborn genetic diseases

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 20, 2021
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:: RCV002426481.2

Allele description [Variation Report for NM_014874.4(MFN2):c.827A>G (p.Gln276Arg)]

NM_014874.4(MFN2):c.827A>G (p.Gln276Arg)

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.827A>G (p.Gln276Arg)

HGVS:

NC_000001.11:g.12001411A>G
NG_007945.1:g.26231A>G
NM_001127660.2:c.827A>G
NM_014874.4:c.827A>GMANE SELECT
NP_001121132.1:p.Gln276Arg
NP_001121132.1:p.Gln276Arg
NP_055689.1:p.Gln276Arg
LRG_255t1:c.827A>G
LRG_255:g.26231A>G
NC_000001.10:g.12061468A>G
NM_001127660.1:c.827A>G
NM_014874.3:c.827A>G
O95140:p.Gln276Arg

Protein change:

Q276R; GLN276ARG

Links:

UniProtKB: O95140#VAR_029878; OMIM: 608507.0010; dbSNP: rs119103264

NCBI 1000 Genomes Browser:

rs119103264

Molecular consequence:

NM_001127660.2:c.827A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.827A>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
SCV002681453	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 20, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16437557, 31372974, 31832804 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002681453

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 20, 2021)

germline

clinical testing

PubMed (3)
[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

Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.

Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM.

Ann Neurol. 2006 Feb;59(2):276-81.

PubMed [citation]

PMID:: 16437557

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot-Marie-Tooth disease.

Chen CX, Dong HL, Wei Q, Li LX, Yu H, Li JQ, Liu GL, Li HF, Bai G, Ma H, Wu ZY.

Clin Genet. 2019 Nov;96(5):439-448. doi: 10.1111/cge.13616. Epub 2019 Aug 8.

PubMed [citation]

PMID:: 31372974

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002681453.2

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

Description

The p.Q276R variant (also known as c.827A>G), located in coding exon 7 of the MFN2 gene, results from an A to G substitution at nucleotide position 827. The glutamine at codon 276 is replaced by arginine, an amino acid with highly similar properties. This variant has been detected in multiple individuals with Charcot-Marie-Tooth disease, including an individual with axonal neuropathy and optic atrophy; however, clinical details were limited (Züchner S et al. Ann Neurol, 2006 Feb;59:276-81; Chen CX et al. Clin Genet, 2019 11;96:439-448; Lin S et al. Neurogenetics, 2020 04;21:79-86). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 7, 2024

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