ClinVar Miner

Submissions for variant NM_020956.2(PRX):c.*1595C>T (rs574861276)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703893 SCV000832819 pathogenic Charcot-Marie-Tooth disease type 4 2018-04-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PRX gene (p.Arg464*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 998 amino acids of the PRX protein. This variant is present in population databases (rs574861276, ExAC 0.01%). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease, type 4F (PMID: 27862672). A different truncation (p.Cys715*) that lies downstream of this variant has been determined to be pathogenic (PMID: 12112076). This suggests that deletion of this region of the PRX protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286834 SCV001473453 pathogenic none provided 2020-02-20 criteria provided, single submitter clinical testing The PRX c.1390C>T; p.Arg464Ter variant (rs574861276) is reported in the literature in three individuals affected with Charcot-Marie-Tooth disease (Dohrn 2017, Vill 2017, Sun 2017). This variant is reported as pathogenic in ClinVar (Variation ID: 580375). At ARUP, this variant was detected in trans with another PRX variant c.1043dupG; p.Glu349fs in two siblings affected with CMT type 4F and Dejerine-Sottas disease. This variant induces an early termination codon and is predicted to result in a truncated protein. Based on available information, this variant is considered to be pathogenic. References: Dohrn et al. Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. J Neurochem. 2017 Dec;143(5):507-522. Vill et al. Jumping Mechanography as a Complementary Testing Tool for Motor Function in Children with Hereditary Motor and Sensory Neuropathy. Neuropediatrics. 2017 Dec;48(6):420-425. Sun et al. Clinical and genetic spectra of Charcot-Marie-Tooth disease in Chinese Han patients. J Peripher Nerv Syst. 2017 Mar;22(1):13-18.

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