U.S. flag

An official website of the United States government

NM_014874.4(MFN2):c.262A>T (p.Ile88Phe) AND Charcot-Marie-Tooth disease type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 1, 2020
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:
RCV000809868.9

Allele description [Variation Report for NM_014874.4(MFN2):c.262A>T (p.Ile88Phe)]

NM_014874.4(MFN2):c.262A>T (p.Ile88Phe)

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.262A>T (p.Ile88Phe)
HGVS:
  • NC_000001.11:g.11992641A>T
  • NG_007945.1:g.17461A>T
  • NM_001127660.2:c.262A>T
  • NM_014874.4:c.262A>TMANE SELECT
  • NP_001121132.1:p.Ile88Phe
  • NP_055689.1:p.Ile88Phe
  • NP_055689.1:p.Ile88Phe
  • LRG_255t1:c.262A>T
  • LRG_255:g.17461A>T
  • LRG_255p1:p.Ile88Phe
  • NC_000001.10:g.12052698A>T
  • NM_014874.3:c.262A>T
Protein change:
I88F
Links:
dbSNP: rs1569816194
NCBI 1000 Genomes Browser:
rs1569816194
Molecular consequence:
  • NM_001127660.2:c.262A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014874.4:c.262A>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

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
SCV000950048Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 1, 2020) 		germlineclinical testing

PubMed (2)
[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

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]
PMID:
26392352
PMCID:
PMC4578331

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000950048.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 26392352, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 653992). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 88 of the MFN2 protein (p.Ile88Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15").

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

Last Updated: Sep 29, 2024