ClinVar Miner

Submissions for variant NM_016156.6(MTMR2):c.1090C>T (p.Arg364Ter)

gnomAD frequency: 0.00001  dbSNP: rs776757548
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cirak Lab, University Hospital Cologne RCV000844881 SCV000965699 pathogenic Charcot-Marie-Tooth disease type 4B1 2019-04-01 criteria provided, single submitter research This variant was observed as a homozygote.
Mendelics RCV000844881 SCV002517743 pathogenic Charcot-Marie-Tooth disease type 4B1 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002453928 SCV002738135 pathogenic Inborn genetic diseases 2021-05-03 criteria provided, single submitter clinical testing The p.R364* pathogenic mutation (also known as c.1090C>T), located in coding exon 10 of the MTMR2 gene, results from a C to T substitution at nucleotide position 1090. This changes the amino acid from an arginine to a stop codon within coding exon 10. This variant was detected as homozygous in two Iranian siblings with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity (Wang H et al. Front Neurosci, 2019 Oct;13:974), and in one individual of Portugese descent with a CMT4B phenotype (Pareyson D et al. Ann Neurol, 2019 07;86:55-67). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV003744669 SCV004534197 pathogenic Charcot-Marie-Tooth disease type 4 2023-08-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 684410). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 31070812, 31680794). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg364*) in the MTMR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTMR2 are known to be pathogenic (PMID: 10802647).

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