ClinVar Miner

Submissions for variant NM_181882.2(PRX):c.1102C>T (p.Arg368Ter) (rs104894715)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760443 SCV000890326 pathogenic not provided 2018-10-11 criteria provided, single submitter clinical testing The R368X nonsense variant in the PRX gene has been reported previously in an individual with Dejerine-Sottas neuropathy who had a second variant identified on the opposite PRX allele (in trans) (Boerkoel et al., 2001). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 1094 amino acids of the protein are lost. The R368X variant is not observed in large population cohorts (Lek et al., 2016).
Invitae RCV000688310 SCV000815915 pathogenic Charcot-Marie-Tooth disease type 4 2018-11-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PRX gene (p.Arg368*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1094 amino acids (~75%) of the PRX protein. This variant is present in population databases (rs104894715, ExAC 0.01%). This variant has been reported in combination with another PRX variant in an individual affected with Dejerine-Sottas syndrome (PMID: 11133365). ClinVar contains an entry for this variant (Variation ID: 4789). A different truncation (p.Arg1070*) that lies downstream of this variant has been determined to be pathogenic (PMID: 15197604, 16770524, 22847150, 26059842). 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.
OMIM RCV000005055 SCV000025231 pathogenic Autosomal recessive Dejerine-Sottas syndrome 2001-02-01 no assertion criteria provided literature only

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