Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000803152 | SCV000943013 | uncertain significance | Primary ciliary dyskinesia | 2022-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 63 of the CCNO protein (p.Ser63Pro). This variant is present in population databases (rs377241996, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CCNO-related conditions. ClinVar contains an entry for this variant (Variation ID: 648428). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CCNO protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| ARUP Laboratories, |
RCV003746555 | SCV004563138 | uncertain significance | Primary ciliary dyskinesia 29 | 2024-11-04 | criteria provided, single submitter | clinical testing | The CCNO c.187T>C; p.Ser63Pro variant (rs377241996), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 648428). This variant is found in the general population with an overall allele frequency of 0.047% (124/263166 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.073). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Ambry Genetics | RCV004601283 | SCV005096544 | uncertain significance | Inborn genetic diseases | 2024-04-12 | criteria provided, single submitter | clinical testing | The c.187T>C (p.S63P) alteration is located in exon 1 (coding exon 1) of the CCNO gene. This alteration results from a T to C substitution at nucleotide position 187, causing the serine (S) at amino acid position 63 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV005056572 | SCV005690074 | uncertain significance | not provided | 2024-08-03 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |