NM_014874.4(MFN2):c.880C>T (p.Arg294Ter) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 30, 2023
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:: RCV001062964.5

Allele description [Variation Report for NM_014874.4(MFN2):c.880C>T (p.Arg294Ter)]

NM_014874.4(MFN2):c.880C>T (p.Arg294Ter)

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.880C>T (p.Arg294Ter)

HGVS:

NC_000001.11:g.12001464C>T
NG_007945.1:g.26284C>T
NM_001127660.2:c.880C>T
NM_014874.4:c.880C>TMANE SELECT
NP_001121132.1:p.Arg294Ter
NP_055689.1:p.Arg294Ter
LRG_255t1:c.880C>T
LRG_255:g.26284C>T
NC_000001.10:g.12061521C>T
NC_000001.10:g.12061521C>T
NM_014874.3:c.880C>T

Protein change:

R294*

Links:

dbSNP: rs866604005

NCBI 1000 Genomes Browser:

rs866604005

Molecular consequence:

NM_001127660.2:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014874.4:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001227790	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 30, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 27549087, 16714318, 16835246, 21715711, 23781337, 26955893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001227790

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 30, 2023)

germline

clinical testing

PubMed (7)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Improving diagnosis of inherited peripheral neuropathies through gene panel analysis.

Laššuthová P, Šafka Brožková D, Krůtová M, Neupauerová J, Haberlová J, Mazanec R, Dřímal P, Seeman P.

Orphanet J Rare Dis. 2016 Aug 22;11(1):118. doi: 10.1186/s13023-016-0500-5.

PubMed [citation]

PMID:: 27549087
PMCID:: PMC4994270

MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2.

Verhoeven K, Claeys KG, Züchner S, Schröder JM, Weis J, Ceuterick C, Jordanova A, Nelis E, De Vriendt E, Van Hul M, Seeman P, Mazanec R, Saifi GM, Szigeti K, Mancias P, Butler IJ, Kochanski A, Ryniewicz B, De Bleecker J, Van den Bergh P, Verellen C, Van Coster R, et al.

Brain. 2006 Aug;129(Pt 8):2093-102. Epub 2006 May 19.

PubMed [citation]

PMID:: 16714318

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001227790.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 857318). This premature translational stop signal has been observed in individual(s) with inherited peripheral neuropathy (PMID: 27549087). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg294*) in the MFN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MFN2 are known to be pathogenic (PMID: 16714318, 16835246, 21715711, 23781337, 26955893).

#	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: Sep 29, 2024

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