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NM_014874.4(MFN2):c.1067C>A (p.Thr356Asn) AND Charcot-Marie-Tooth disease type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 10, 2018
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:
RCV000817662.7

Allele description [Variation Report for NM_014874.4(MFN2):c.1067C>A (p.Thr356Asn)]

NM_014874.4(MFN2):c.1067C>A (p.Thr356Asn)

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.1067C>A (p.Thr356Asn)
HGVS:
  • NC_000001.11:g.12002010C>A
  • NG_007945.1:g.26830C>A
  • NM_001127660.2:c.1067C>A
  • NM_014874.4:c.1067C>AMANE SELECT
  • NP_001121132.1:p.Thr356Asn
  • NP_055689.1:p.Thr356Asn
  • NP_055689.1:p.Thr356Asn
  • LRG_255t1:c.1067C>A
  • LRG_255:g.26830C>A
  • LRG_255p1:p.Thr356Asn
  • NC_000001.10:g.12062067C>A
  • NM_014874.3:c.1067C>A
Protein change:
T356N
Links:
dbSNP: rs1569853976
NCBI 1000 Genomes Browser:
rs1569853976
Molecular consequence:
  • NM_001127660.2:c.1067C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014874.4:c.1067C>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000958239Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 10, 2018) 		germlineclinical testing

PubMed (3)
[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

MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients.

Xie Y, Li X, Liu L, Hu Z, Huang S, Zhan Y, Zi X, Xia K, Tang B, Zhang R.

J Peripher Nerv Syst. 2016 Mar;21(1):38-44. doi: 10.1111/jns.12159.

PubMed [citation]
PMID:
26801520

A novel mutation of the MFN2 gene in a Chinese family with Charcot-Marie-Tooth disease.

Wang YW, Han WT, Jiang M, Lu CX, Li XF, Zhang X, Li JX.

Genet Mol Res. 2012 May 18;11(2):1454-9. doi: 10.4238/2012.May.18.5.

PubMed [citation]
PMID:
22653593
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000958239.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Thr356 amino acid residue in MFN2. Other variants that disrupt this residue have been observed in affected individuals (PMID: 26801520, 22653593), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MFN2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with asparagine at codon 356 of the MFN2 protein (p.Thr356Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine.

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

Last Updated: Sep 29, 2024