Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cirak Lab, |
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). |