This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3.
ClinVar Genomic variation as it relates to human health
NM_014874.4(MFN2):c.1085C>T (p.Thr362Met)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic/Likely pathogenic
7 out of 11 submissions contributed to this classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
11
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_014874.4(MFN2):c.1085C>T (p.Thr362Met)
Variation ID: 30738 Accession: VCV000030738.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p36.22 1: 12002028 (GRCh38) [ NCBI UCSC ] 1: 12062085 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 4, 2016 Feb 25, 2025 Oct 20, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_014874.4:c.1085C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055689.1:p.Thr362Met missense NM_001127660.2:c.1085C>T NP_001121132.1:p.Thr362Met missense NC_000001.11:g.12002028C>T NC_000001.10:g.12062085C>T NG_007945.1:g.26848C>T LRG_255:g.26848C>T LRG_255t1:c.1085C>T LRG_255p1:p.Thr362Met O95140:p.Thr362Met - Protein change
- T362M
- Other names
-
NM_001127660.1:c.1085C>T(p.Thr362Met)
NM_014874.3:c.1085C>T(p.Thr362Met)
- Canonical SPDI
- NC_000001.11:12002027:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| MFN2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
1328 | 1436 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, single submitter
|
Dec 1, 2020 | RCV000023716.6 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jun 20, 2019 | RCV001198485.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 20, 2024 | RCV001388766.8 | |
| Likely pathogenic (3) |
criteria provided, single submitter
|
Apr 16, 2018 | RCV000240513.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 6, 2022 | RCV002472935.2 | |
| Likely pathogenic (2) |
criteria provided, single submitter
|
- | RCV000857102.2 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Oct 19, 2020 | RCV002415428.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(-)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Charcot-Marie-Tooth disease
Affected status: yes
Allele origin:
germline
|
Molecular Genetics Laboratory, London Health Sciences Centre
Accession: SCV001336794.1
First in ClinVar: Jun 15, 2020 Last updated: Jun 15, 2020 |
|
|
|
Likely pathogenic
(Jun 20, 2019)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Neuropathy, hereditary motor and sensory, type 6A
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369432.2
First in ClinVar: Jul 06, 2020 Last updated: Jul 06, 2020 |
Comment:
This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3.
|
|
|
Pathogenic
(Dec 01, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Charcot-Marie-Tooth disease type 2A2
Affected status: yes
Allele origin:
germline
|
CMT Laboratory, Bogazici University
Accession: SCV001548312.1
First in ClinVar: Apr 03, 2021 Last updated: Apr 03, 2021 |
Number of individuals with the variant: 1
Family history: yes
Secondary finding: no
|
|
|
Likely pathogenic
(Oct 19, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002724932.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
|
|
|
Likely pathogenic
(Apr 16, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: curation
|
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;
Affected status: unknown
Allele origin:
germline
|
SIB Swiss Institute of Bioinformatics
Accession: SCV000787447.1
First in ClinVar: Jul 21, 2018 Last updated: Jul 21, 2018 |
Comment:
This variant is interpreted as a Likely Pathogenic, for Charcot-Marie-Tooth disease, axonal, type 2A2B, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => … (more)
This variant is interpreted as a Likely Pathogenic, for Charcot-Marie-Tooth disease, axonal, type 2A2B, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:21715711). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => PS4 downgraded in strength to Moderate (PMID:16835246, 21715711, 18458227). (less)
|
|
|
Pathogenic
(Jul 06, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV002771026.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is primarily reported in severe, early onset, autosomal recessive … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is primarily reported in severe, early onset, autosomal recessive form of Charcot-Marie-Tooth type 2A (CMT2A; PMID: 9736777 15786415, 17932099, 18337730, 21387378, 24037712, 28662944). Heterozygous members of these families are reported as asymptomatic. However, this variant has also been reported in autosomal dominant CMT2A (PMID: 16835246, 33475540). Computational tools predict that this variant is damaging. (less)
|
|
|
Pathogenic
(Oct 20, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Charcot-Marie-Tooth disease type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001589889.5
First in ClinVar: May 10, 2021 Last updated: Feb 25, 2025 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 362 of the MFN2 protein (p.Thr362Met). … (more)
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 362 of the MFN2 protein (p.Thr362Met). This variant is present in population databases (rs387906991, gnomAD 0.02%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 16835246, 18458227, 21715711, 26114802). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30738). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 25, 2018)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: clinical testing
|
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Cologne University
Accession: SCV000787795.1
First in ClinVar: Jul 21, 2018 Last updated: Jul 21, 2018 |
|
|
|
Pathogenic
(Jul 12, 2011)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: literature only
|
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2A2A
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000045007.4
First in ClinVar: Apr 04, 2013 Last updated: Jun 10, 2023 |
Comment on evidence:
In a Korean mother and daughter with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), Chung et al. (2006) identified a heterozygous 1085C-T transition in the MFN2 gene, resulting … (more)
In a Korean mother and daughter with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), Chung et al. (2006) identified a heterozygous 1085C-T transition in the MFN2 gene, resulting in a thr362-to-met (T362M) substitution. The patients had late onset and a mild phenotype. In 2 adult Italian sibs with autosomal recessive inheritance of severe early-onset CMT2A2B (617087), Polke et al. (2011) identified compound heterozygosity for 2 mutations in the MFN2 gene: a T362M substitution on the maternal allele, and a 3-bp in-frame deletion (113delAGA; 608507.0020) resulting in a deletion of lys38 (lys38del), presumably from the paternal allele, although no DNA was available from the deceased father. The patients had onset of foot drop and upper and lower limb weakness at age 3 years. They also had decreased pinprick and vibration senses, more severe in the lower limbs, kyphosis, pale optic discs, visual loss, severe facial weakness, and respiratory muscle weakness. One had hearing loss and vocal cord palsy. Both were wheelchair-bound. Nerve conduction studies showed absence of nerve conduction in 1 patient tested. Neither parent was affected. Polke et al. (2011) noted that the T362M mutation had also been reported in families with dominant transmission, suggesting that it has a dominant-negative effect; the pathogenic effect of the lys38 deletion mutation was unknown, although it was not found in 550 control chromosomes. In a 32-year-old woman (CMT742) with autosomal recessive CMT2A2B, Nicholson et al. (2008) identified compound heterozygosity for 2 missense mutations in the MFN2 gene: T362M and A164V (608507.0021). (less)
|
|
|
Pathogenic
(Jul 12, 2011)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: literature only
|
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2A2B, AUTOSOMAL RECESSIVE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000298224.2
First in ClinVar: Sep 04, 2016 Last updated: Jun 10, 2023 |
Comment on evidence:
In a Korean mother and daughter with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), Chung et al. (2006) identified a heterozygous 1085C-T transition in the MFN2 gene, resulting … (more)
In a Korean mother and daughter with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), Chung et al. (2006) identified a heterozygous 1085C-T transition in the MFN2 gene, resulting in a thr362-to-met (T362M) substitution. The patients had late onset and a mild phenotype. In 2 adult Italian sibs with autosomal recessive inheritance of severe early-onset CMT2A2B (617087), Polke et al. (2011) identified compound heterozygosity for 2 mutations in the MFN2 gene: a T362M substitution on the maternal allele, and a 3-bp in-frame deletion (113delAGA; 608507.0020) resulting in a deletion of lys38 (lys38del), presumably from the paternal allele, although no DNA was available from the deceased father. The patients had onset of foot drop and upper and lower limb weakness at age 3 years. They also had decreased pinprick and vibration senses, more severe in the lower limbs, kyphosis, pale optic discs, visual loss, severe facial weakness, and respiratory muscle weakness. One had hearing loss and vocal cord palsy. Both were wheelchair-bound. Nerve conduction studies showed absence of nerve conduction in 1 patient tested. Neither parent was affected. Polke et al. (2011) noted that the T362M mutation had also been reported in families with dominant transmission, suggesting that it has a dominant-negative effect; the pathogenic effect of the lys38 deletion mutation was unknown, although it was not found in 550 control chromosomes. In a 32-year-old woman (CMT742) with autosomal recessive CMT2A2B, Nicholson et al. (2008) identified compound heterozygosity for 2 missense mutations in the MFN2 gene: T362M and A164V (608507.0021). (less)
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Uncertain significance
(Aug 14, 2019)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: research
|
Charcot-Marie-Tooth disease
Affected status: yes
Allele origin:
germline
|
Genesis Genome Database
Accession: SCV000999676.1
First in ClinVar: Dec 17, 2019 Last updated: Dec 17, 2019 |
|
|
| click to load more submissions click to collapse | |||||
Comment:
Comment:
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.
Comment:
This variant is interpreted as a Likely Pathogenic, for Charcot-Marie-Tooth disease, axonal, type 2A2B, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:21715711). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => PS4 downgraded in strength to Moderate (PMID:16835246, 21715711, 18458227).
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is primarily reported in severe, early onset, autosomal recessive form of Charcot-Marie-Tooth type 2A (CMT2A; PMID: 9736777 15786415, 17932099, 18337730, 21387378, 24037712, 28662944). Heterozygous members of these families are reported as asymptomatic. However, this variant has also been reported in autosomal dominant CMT2A (PMID: 16835246, 33475540). Computational tools predict that this variant is damaging.
Comment:
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 362 of the MFN2 protein (p.Thr362Met). This variant is present in population databases (rs387906991, gnomAD 0.02%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 16835246, 18458227, 21715711, 26114802). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30738). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. For these reasons, this variant has been classified as Pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3.
Comment:
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.
Comment:
This variant is interpreted as a Likely Pathogenic, for Charcot-Marie-Tooth disease, axonal, type 2A2B, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:21715711). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => PS4 downgraded in strength to Moderate (PMID:16835246, 21715711, 18458227).
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is primarily reported in severe, early onset, autosomal recessive form of Charcot-Marie-Tooth type 2A (CMT2A; PMID: 9736777 15786415, 17932099, 18337730, 21387378, 24037712, 28662944). Heterozygous members of these families are reported as asymptomatic. However, this variant has also been reported in autosomal dominant CMT2A (PMID: 16835246, 33475540). Computational tools predict that this variant is damaging.
Comment:
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 362 of the MFN2 protein (p.Thr362Met). This variant is present in population databases (rs387906991, gnomAD 0.02%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 16835246, 18458227, 21715711, 26114802). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30738). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Analysis of the conformational changes caused by the mutations in mitofusin2 gene by Insilico approach. | Rasheed MA | JPMA. The Journal of the Pakistan Medical Association | 2020 | PMID: 33475540 |
| Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. | Pipis M | Brain : a journal of neurology | 2020 | PMID: 33415332 |
| Yield of next-generation neuropathy gene panels in axonal neuropathies. | Lee DC | Journal of the peripheral nervous system : JPNS | 2019 | PMID: 31701603 |
| Targeted sequencing with expanded gene profile enables high diagnostic yield in non-5q-spinal muscular atrophies. | Karakaya M | Human mutation | 2018 | PMID: 29858556 |
| Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases. | Plutino M | BMC medical genetics | 2018 | PMID: 29625556 |
| MFN2 deletion of exons 7 and 8: founder mutation in the UK population. | Carr AS | Journal of the peripheral nervous system : JPNS | 2015 | PMID: 26114802 |
| A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients. | Choi BO | Clinical genetics | 2015 | PMID: 24863639 |
| Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease. | Bergamin G | Neuromolecular medicine | 2014 | PMID: 24819634 |
| Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations. | Polke JM | Neurology | 2011 | PMID: 21715711 |
| Histopathological findings in hereditary motor and sensory neuropathy of axonal type with onset in early childhood associated with mitofusin 2 mutations. | Vallat JM | Journal of neuropathology and experimental neurology | 2008 | PMID: 18957892 |
| Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations. | Nicholson GA | Neurology | 2008 | PMID: 18458227 |
| Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. | Chung KW | Brain : a journal of neurology | 2006 | PMID: 16835246 |
| click to load more citations click to collapse | ||||
Text-mined citations for rs387906991 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Mar 16, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.