NM_014874.4(MFN2):c.2119C>T (p.Arg707Trp) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jun 26, 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:: RCV000199654.40

Allele description [Variation Report for NM_014874.4(MFN2):c.2119C>T (p.Arg707Trp)]

NM_014874.4(MFN2):c.2119C>T (p.Arg707Trp)

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.2119C>T (p.Arg707Trp)

Other names:

p.R707W:CGG>TGG; NM_001127660.1(MFN2):c.2119C>T(p.Arg707Trp); NM_014874.3(MFN2):c.2119C>T(p.Arg707Trp)

HGVS:

NC_000001.11:g.12009641C>T
NG_007945.1:g.34461C>T
NM_001127660.1:c.2119C>T
NM_001127660.2:c.2119C>T
NM_014874.4:c.2119C>TMANE SELECT
NP_001121132.1:p.Arg707Trp
NP_055689.1:p.Arg707Trp
NP_055689.1:p.Arg707Trp
LRG_255t1:c.2119C>T
LRG_255:g.34461C>T
LRG_255p1:p.Arg707Trp
NC_000001.10:g.12069698C>T
NM_014874.3:c.2119C>T
NM_014874.4:c.2119C>T
p.Arg707Trp

Protein change:

R707W; ARG707TRP

Links:

OMIM: 608507.0013; dbSNP: rs119103267

NCBI 1000 Genomes Browser:

rs119103267

Molecular consequence:

NM_001127660.2:c.2119C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.2119C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000251722	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 26, 2024)	germline	clinical testing	Citation Link,
SCV000705467	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jan 23, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18458227, 20008656, 26085578 Citation Link,
SCV001961079	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2024)	germline	clinical testing	Citation Link,
SCV002024345	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 13, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005199123	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations.

Nicholson GA, Magdelaine C, Zhu D, Grew S, Ryan MM, Sturtz F, Vallat JM, Ouvrier RA.

Neurology. 2008 May 6;70(19):1678-81. doi: 10.1212/01.wnl.0000311275.89032.22.

PubMed [citation]

PMID:: 18458227

Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

Calvo J, Funalot B, Ouvrier RA, Lazaro L, Toutain A, De Mas P, Bouche P, Gilbert-Dussardier B, Arne-Bes MC, Carrière JP, Journel H, Minot-Myhie MC, Guillou C, Ghorab K, Magy L, Sturtz F, Vallat JM, Magdelaine C.

Arch Neurol. 2009 Dec;66(12):1511-6. doi: 10.1001/archneurol.2009.284.

PubMed [citation]

PMID:: 20008656

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000251722.16

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Functional studies show that R707W alters gene product function and signaling (PMID: 30158064); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28492532, 22492563, 25025039, 28251916, 26306937, 24126688, 20350294, 26085578, 26114802, 36722855, 31589614, 31980526, 32376792, 29867446, 32916636, 33502018, 34426522, 29358271, 26392352, 25231362, 35641312, 20008656, MarquesAJ2024[Article], 35305867, 35468369, 38887266, FossdeFreitaMC2023[Abstract], 37536398, 33415332, 28414270, 18458227, 30158064)

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

From Eurofins Ntd Llc (ga), SCV000705467.2

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001961079.20

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

Description

MFN2: PM3:Very Strong, PM2:Supporting, PM5:Supporting, PP1, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002024345.3

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

#	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

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199123.1

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

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

Last Updated: Nov 3, 2024

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