Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002022560 | SCV002288305 | likely pathogenic | not provided | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1286 of the CPLANE1 protein (p.Arg1286His). This variant is present in population databases (rs139464953, gnomAD 0.004%). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 29955609, 30403813). ClinVar contains an entry for this variant (Variation ID: 1502898). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CPLANE1 protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479389 | SCV004223474 | uncertain significance | not specified | 2023-11-07 | criteria provided, single submitter | clinical testing | Variant summary: CPLANE1 c.3857G>A (p.Arg1286His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 282504 control chromosomes (gnomAD). c.3857G>A has been reported in the literature in compound heterozygous individuals affected with Joubert Syndrome And Related Disorders (Xiang_2018, Nuovo_2020, Zhang_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30403813, 29955609, 34091942, 32047782). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |