Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000990217 | SCV001141087 | pathogenic | Spinocerebellar ataxia 46 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001008813 | SCV001168614 | likely pathogenic | not provided | 2018-11-23 | criteria provided, single submitter | clinical testing | The c.3198delT variant in the PRX gene has been reported previously in the homozygous state in association with Charcot-Marie-Tooth type 4F (Renouil et al., 2013). The c.3198delT variant causes a frameshift starting with codon Phenylalanine 1066, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 61 of the new reading frame, denoted p.Phe1066LeufsX61. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 396 amino acids are lost and replaced with 60 incorrect amino acids. The c.3198delT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3198delT as a likely pathogenic variant. |
| Molecular Genetics Laboratory, |
RCV000789548 | SCV001335823 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV003117579 | SCV003786314 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2022-05-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRX protein in which other variant(s) (p.Arg1070*) have been determined to be pathogenic (PMID: 15197604, 15469949, 16770524, 22847150, 26059842). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 637402). This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 24011642, 32376792). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1066Leufs*61) in the PRX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 396 amino acid(s) of the PRX protein. |
| Inherited Neuropathy Consortium | RCV000789548 | SCV000928904 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |