Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000438829 | SCV000535549 | pathogenic | not provided | 2017-01-16 | criteria provided, single submitter | clinical testing | The R424X variant in the C5orf42 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R424X variant was not observed in approximately 2300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R424X as a pathogenic variant. |
| Invitae | RCV000438829 | SCV001584116 | pathogenic | not provided | 2017-09-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg424*) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs755097302, ExAC 0.03%). This variant has not been reported in the literature in individuals with C5orf42-related disease. ClinVar contains an entry for this variant (Variation ID: 392297). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000694430 | SCV002789191 | likely pathogenic | Orofaciodigital syndrome type 6; Joubert syndrome 17 | 2021-11-19 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003147459 | SCV003835005 | pathogenic | Joubert syndrome 17 | 2021-04-24 | criteria provided, single submitter | clinical testing | |
| Department of Neurology, |
RCV001729596 | SCV001571327 | pathogenic | Joubert syndrome 1 | 2021-01-02 | no assertion criteria provided | research | The nonsense variant c.1270C>T (p.Arg424*) in exon 10 resulted in the 2120th base with the change from C to T in the coding region of CPLANE1 , which caused substitution from arginine to a stop codon at the 424th amino acid of the encoded protein, and may cause protein truncation or activate degradation of the mRNA of CPLANE1 via nonsense mediation, thereby affecting the function of the protein product encoded by CPLANE1 (PVS1). This variant is present in population databases (rs755097302, ExAC 0.03%), and the frequency is G = 0.0001 (PM2). It has not been reported in the literature in individuals, but the ClinVar database contains an entry for this mutation as a "pathogenic variant" (variation ID: 392297) for Oral-facial-digital syndrome VI and Joubert syndrome 17 (PM3_Strong). The father of the proband carries a heterozygous mutation at this locus. According to the available evidence, it is defined as the pathogenic variant (PVS1+PM3_Strong+PM2) based on the 2015 ACMG guidelines. |