Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000817262 | SCV000957812 | uncertain significance | Primary ciliary dyskinesia | 2023-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 460 of the CCDC40 protein (p.Phe460Tyr). 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. 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 CCDC40 protein function. ClinVar contains an entry for this variant (Variation ID: 660127). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. This variant is present in population databases (rs201576715, gnomAD 0.04%). |
| Ambry Genetics | RCV000817262 | SCV002699798 | uncertain significance | Primary ciliary dyskinesia | 2018-07-27 | criteria provided, single submitter | clinical testing | The p.F460Y variant (also known as c.1379T>A), located in coding exon 9 of the CCDC40 gene, results from a T to A substitution at nucleotide position 1379. The phenylalanine at codon 460 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |