Submissions for variant NM_020956.2(PRX):c.*1379C>T (rs773009397)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235669	SCV000293044	pathogenic	not provided	2015-08-25	criteria provided, single submitter	clinical testing	The R392X nonsense variant in the PRX gene has been reported previously in an individual with Dejerine-Sottas neuropathy who had a second variant on the opposite allele (Choi et al., 2013). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is predicted to cause loss of normal protein function through protein truncation as the last 1,070 amino acids are lost. Therefore, R392X is interpreted to be a pathogenic variant.
Invitae	RCV001057364	SCV001221851	pathogenic	Charcot-Marie-Tooth disease type 4	2019-06-04	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the PRX gene (p.Arg392). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1070 amino acids of the PRX protein. This variant is present in population databases (rs773009397, ExAC 0.02%). This variant has been observed in individual(s) with Dejerine-Sottas neuropathy (PMID: 25628743). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 245870). This variant disrupts the C-terminus of the PRX protein. Other variant(s) that disrupt this region (p.Arg1070) have been determined to be pathogenic (PMID: 15197604, 15469949, 16770524, 22847150, 26059842, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium	RCV000789534	SCV000928890	uncertain significance	Dejerine-Sottas disease		no assertion criteria provided	literature only

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