Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000236836 | SCV000255810 | pathogenic | not provided | 2019-03-11 | criteria provided, single submitter | clinical testing | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity. |
| Gene |
RCV000236836 | SCV000293535 | pathogenic | not provided | 2018-12-06 | criteria provided, single submitter | clinical testing | The R953X variant in the PRX gene has been reported previously in the compound heterozygous state in an individual with Dejerine-Sottas Neuropathy (Boerkoel et al., 2001). This variant is predicted to cause loss of normal protein function through protein truncation, as the last 509 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014). The R953X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R953X as a pathogenic variant. |
| Invitae | RCV000458979 | SCV000551417 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2018-12-19 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the last exon of the PRX mRNA at codon 953 (p.Arg953*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 509 amino acids (~35%) of the PRX protein. This variant is present in population databases (rs104894714, ExAC 0.02%). This variant has been reported in a family affected with Dejerine-Sottas syndrome (PMID: 11133365). A different truncation downstream of this variant (p.R1070*) has been determined to be pathogenic (PMID: 15197604, 22847150, 16770524). 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. |
| Baylor Genetics | RCV000201141 | SCV000807618 | pathogenic | Charcot-Marie-Tooth disease, demyelinating, type 4F | 2017-09-01 | criteria provided, single submitter | clinical testing | This variant has been previously reported as disease-causing and was found once in our laboratory homozygous in a 14-year-old female with Charcot Marie Tooth disease. Heterozygotes are expected to be asymptomatic carriers. |
| OMIM | RCV000005053 | SCV000025229 | pathogenic | Autosomal recessive Dejerine-Sottas syndrome | 2001-02-01 | no assertion criteria provided | literature only |