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NM_014874.4(MFN2):c.1085C>T (p.Thr362Met) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 19, 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:
RCV002415428.2

Allele description [Variation Report for NM_014874.4(MFN2):c.1085C>T (p.Thr362Met)]

NM_014874.4(MFN2):c.1085C>T (p.Thr362Met)

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.1085C>T (p.Thr362Met)
Other names:
NM_001127660.1:c.1085C>T(p.Thr362Met); NM_014874.3:c.1085C>T(p.Thr362Met)
HGVS:
  • NC_000001.11:g.12002028C>T
  • NG_007945.1:g.26848C>T
  • NM_001127660.2:c.1085C>T
  • NM_014874.4:c.1085C>TMANE SELECT
  • NP_001121132.1:p.Thr362Met
  • NP_001121132.1:p.Thr362Met
  • NP_055689.1:p.Thr362Met
  • NP_055689.1:p.Thr362Met
  • LRG_255t1:c.1085C>T
  • LRG_255:g.26848C>T
  • LRG_255p1:p.Thr362Met
  • NC_000001.10:g.12062085C>T
  • NM_001127660.1:c.1085C>T
  • NM_014874.3:c.1085C>T
  • O95140:p.Thr362Met
Protein change:
T362M; THR362MET
Links:
UniProtKB: O95140#VAR_076897; OMIM: 608507.0019; dbSNP: rs387906991
NCBI 1000 Genomes Browser:
rs387906991
Molecular consequence:
  • NM_001127660.2:c.1085C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014874.4:c.1085C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002724932Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Oct 19, 2020) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations.

Polke JM, Laurá M, Pareyson D, Taroni F, Milani M, Bergamin G, Gibbons VS, Houlden H, Chamley SC, Blake J, Devile C, Sandford R, Sweeney MG, Davis MB, Reilly MM.

Neurology. 2011 Jul 12;77(2):168-73. doi: 10.1212/WNL.0b013e3182242d4d. Epub 2011 Jun 29.

PubMed [citation]
PMID:
21715711
PMCID:
PMC3140074

MFN2 deletion of exons 7 and 8: founder mutation in the UK population.

Carr AS, Polke JM, Wilson J, Pelayo-Negro AL, Laura M, Nanji T, Holt J, Vaughan J, Rankin J, Sweeney MG, Blake J, Houlden H, Reilly MM.

J Peripher Nerv Syst. 2015 Jun;20(2):67-71. doi: 10.1111/jns.12117.

PubMed [citation]
PMID:
26114802
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002724932.2

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

Description

The p.T362M variant (also known as c.1085C>T), located in coding exon 9 of the MFN2 gene, results from a C to T substitution at nucleotide position 1085. The threonine at codon 362 is replaced by methionine, an amino acid with similar properties. This alteration has been reported homozygous in an individual with Charcot-Marie-Tooth disease (CMT) type 2 (CMT2)(Karakaya M et al. Hum Mutat, 2018 09;39:1284-1298) and has been detected in trans with another MFN2 pathogenic mutation in multiple unrelated individuals with CMT2 (Carr AS et al. J Peripher Nerv Syst, 2015 Jun;20:67-71). This alteration has also been reported to segregate with disease in a family with CMT2 (Polke JM et al. Neurology, 2011 Jul;77:168-73). In addition to the clinical data presented in the literature, this amino acid position is highly conserved in available vertebrate species and is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this variant is expected to be causative of Charcot-Marie-Tooth disease (CMT) type 2A2B when present along with a second pathogenic variant on the other allele; however, its clinical significance for Charcot-Marie-Tooth disease (CMT) type 2A2A and hereditary motor and sensory neuropathy VIA is unclear.

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

Last Updated: Sep 29, 2024