Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000174405 | SCV000225698 | pathogenic | not provided | 2014-12-19 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000174405 | SCV001420911 | pathogenic | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 194120). This variant has not been reported in the literature in individuals affected with CPLANE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr607Leufs*12) in the CPLANE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPLANE1 are known to be pathogenic (PMID: 24178751, 26092869). |
| Fulgent Genetics, |
RCV002492734 | SCV002800332 | likely pathogenic | Orofaciodigital syndrome type 6; Joubert syndrome 17 | 2021-07-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003491928 | SCV004241406 | pathogenic | Joubert syndrome and related disorders | 2023-12-13 | criteria provided, single submitter | clinical testing | Variant summary: CPLANE1 c.1819dupT (p.Tyr607LeufsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 1539920 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CPLANE1 causing Joubert Syndrome And Related Disorders (1.2e-05 vs 0.0015), allowing no conclusion about variant significance. c.1819dupT has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders (Zhang_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 34091942). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |