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NM_014874.4(MFN2):c.310C>T (p.Arg104Trp) AND Charcot-Marie-Tooth disease type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 25, 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:
RCV000556047.9

Allele description [Variation Report for NM_014874.4(MFN2):c.310C>T (p.Arg104Trp)]

NM_014874.4(MFN2):c.310C>T (p.Arg104Trp)

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.310C>T (p.Arg104Trp)
Other names:
p.R104W:CGG>TGG; chr1-11992689-C-T; p.Arg104Trp
HGVS:
  • NC_000001.11:g.11992689C>T
  • NG_007945.1:g.17509C>T
  • NM_001127660.2:c.310C>T
  • NM_014874.4:c.310C>TMANE SELECT
  • NP_001121132.1:p.Arg104Trp
  • NP_001121132.1:p.Arg104Trp
  • NP_055689.1:p.Arg104Trp
  • NP_055689.1:p.Arg104Trp
  • LRG_255t1:c.310C>T
  • LRG_255:g.17509C>T
  • LRG_255p1:p.Arg104Trp
  • NC_000001.10:g.12052746C>T
  • NM_001127660.1:c.310C>T
  • NM_014874.3:c.310C>T
Protein change:
R104W; ARG104TRP
Links:
OMIM: 608507.0014; dbSNP: rs119103268
NCBI 1000 Genomes Browser:
rs119103268
Molecular consequence:
  • NM_001127660.2:c.310C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014874.4:c.310C>T - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000657723Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 25, 2023) 		germlineclinical testing

PubMed (9)
[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

Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

Brockmann K, Dreha-Kulaczewski S, Dechent P, Bönnemann C, Helms G, Kyllerman M, Brück W, Frahm J, Huehne K, Gärtner J, Rautenstrauss B.

J Neurol. 2008 Jul;255(7):1049-58. doi: 10.1007/s00415-008-0847-1. Epub 2008 Apr 21.

PubMed [citation]
PMID:
18425620

Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction.

Del Bo R, Moggio M, Rango M, Bonato S, D'Angelo MG, Ghezzi S, Airoldi G, Bassi MT, Guglieri M, Napoli L, Lamperti C, Corti S, Federico A, Bresolin N, Comi GP.

Neurology. 2008 Dec 9;71(24):1959-66. doi: 10.1212/01.wnl.0000327095.32005.a4. Epub 2008 Oct 22.

PubMed [citation]
PMID:
18946002
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000657723.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 104 of the MFN2 protein (p.Arg104Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 18425620, 18946002, 18957892, 20008656, 21531138, 21840889, 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: 2281). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg104 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22492563). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024