ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.1085C>T (p.Thr362Met) (rs387906991)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000240513 SCV000787447 likely pathogenic Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2A2B 2018-04-16 criteria provided, single submitter curation 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).
Molecular Genetics Laboratory,London Health Sciences Centre RCV000857102 SCV001336794 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198485 SCV001369432 likely pathogenic Hereditary motor and sensory neuropathy with optic atrophy 2019-06-20 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3.
CMT Laboratory,Bogazici University RCV000023716 SCV001548312 pathogenic Charcot-Marie-Tooth disease, type 2A2A 2020-12-01 criteria provided, single submitter clinical testing
Invitae RCV001388766 SCV001589889 pathogenic Charcot-Marie-Tooth disease, type 2 2020-08-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 362 of the MFN2 protein (p.Thr362Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs387906991, ExAC 0.01%). This variant has been observed in the compound heterozygous state in individuals and families with severe, early-onset CMT and has been observed in the heterozygous state in unaffected individuals as well as in individuals with mild, late-onset CMT (PMID: 18458227, 26114802, 21715711, 16835246). ClinVar contains an entry for this variant (Variation ID: 30738). 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: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000023716 SCV000045007 pathogenic Charcot-Marie-Tooth disease, type 2A2A 2011-07-12 no assertion criteria provided literature only
OMIM RCV000240513 SCV000298224 pathogenic Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2A2B 2011-07-12 no assertion criteria provided literature only
Institute of Human Genetics,Cologne University RCV000240513 SCV000787795 pathogenic Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2A2B 2018-04-25 no assertion criteria provided clinical testing
Genesis Genome Database RCV000857102 SCV000999676 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

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