Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813447 | SCV000953807 | uncertain significance | Primary ciliary dyskinesia | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with asparagine at codon 574 of the CCDC40 protein (p.Thr574Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs202093340, ExAC 0.07%). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV000813447 | SCV002716634 | uncertain significance | Primary ciliary dyskinesia | 2020-12-15 | criteria provided, single submitter | clinical testing | The p.T574N variant (also known as c.1721C>A), located in coding exon 11 of the CCDC40 gene, results from a C to A substitution at nucleotide position 1721. The threonine at codon 574 is replaced by asparagine, an amino acid with 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. |
| Fulgent Genetics, |
RCV002495141 | SCV002783833 | uncertain significance | Primary ciliary dyskinesia 15 | 2022-02-25 | criteria provided, single submitter | clinical testing |