U.S. flag

An official website of the United States government

NM_014874.4(MFN2):c.281G>A (p.Arg94Gln) AND Charcot-Marie-Tooth disease type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 28, 2024
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:
RCV000463055.14

Allele description [Variation Report for NM_014874.4(MFN2):c.281G>A (p.Arg94Gln)]

NM_014874.4(MFN2):c.281G>A (p.Arg94Gln)

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.281G>A (p.Arg94Gln)
Other names:
chr1-11992660-G-A
HGVS:
  • NC_000001.11:g.11992660G>A
  • NG_007945.1:g.17480G>A
  • NM_001127660.2:c.281G>A
  • NM_014874.4:c.281G>AMANE SELECT
  • NP_001121132.1:p.Arg94Gln
  • NP_001121132.1:p.Arg94Gln
  • NP_055689.1:p.Arg94Gln
  • NP_055689.1:p.Arg94Gln
  • LRG_255t1:c.281G>A
  • LRG_255:g.17480G>A
  • LRG_255p1:p.Arg94Gln
  • NC_000001.10:g.12052717G>A
  • NM_001127660.1:c.281G>A
  • NM_014874.3:c.281G>A
  • O95140:p.Arg94Gln
Protein change:
R94Q; ARG94GLN
Links:
UniProtKB: O95140#VAR_018609; OMIM: 608507.0001; dbSNP: rs28940291
NCBI 1000 Genomes Browser:
rs28940291
Molecular consequence:
  • NM_001127660.2:c.281G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014874.4:c.281G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000547922Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 28, 2024) 		germlineclinical testing

PubMed (14)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A.

Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schröder JM, Vance JM.

Nat Genet. 2004 May;36(5):449-51. Epub 2004 Apr 4. No abstract available. Erratum in: Nat Genet. 2004 Jun;36(6):660. Battologlu E [corrected to Battaloglu E].

PubMed [citation]
PMID:
15064763

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 (14)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000547922.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (14)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 94 of the MFN2 protein (p.Arg94Gln). This variant is present in population databases (rs28940291, gnomAD 0.0009%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 15064763, 16714318, 17437620, 18996695, 19889647, 24604904, 25025039). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2268). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MFN2 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects MFN2 function (PMID: 17215403, 17296794, 20335458, 20418531, 21285398, 22442078). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024