Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001125959 | SCV001285097 | uncertain significance | Primary ciliary dyskinesia 15 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Invitae | RCV001314515 | SCV001505049 | uncertain significance | Primary ciliary dyskinesia | 2022-07-12 | 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 870 of the CCDC40 protein (p.Arg870His). This variant is present in population databases (rs373717036, gnomAD 0.02%). This missense change has been observed in individual(s) with primary ciliary dyskinesia (PMID: 25619595). ClinVar contains an entry for this variant (Variation ID: 890960). 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 | RCV001314515 | SCV002745537 | uncertain significance | Primary ciliary dyskinesia | 2019-06-20 | criteria provided, single submitter | clinical testing | The p.R870H variant (also known as c.2609G>A), located in coding exon 15 of the CCDC40 gene, results from a G to A substitution at nucleotide position 2609. The arginine at codon 870 is replaced by histidine, an amino acid with highly similar properties. This variant was identified in an adult male with a history of a chronic cough, recurrent respiratory infections, bronchiolitis on lung biopsy, bronchiectasis on chest CT, situs inversus, sinusitis, infertility; electron microscopy identified inner dynein arm defects and axonemal disorganization (Sui W et al. Clin Respir J, 2016 Sep;10:614-21). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear. |