Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000629467 | SCV000750411 | uncertain significance | Primary ciliary dyskinesia | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1059 of the CCDC40 protein (p.Arg1059Gln). This variant is present in population databases (rs200902434, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. ClinVar contains an entry for this variant (Variation ID: 525411). 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. 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 | RCV000629467 | SCV002609271 | uncertain significance | Primary ciliary dyskinesia | 2022-06-12 | criteria provided, single submitter | clinical testing | The p.R1059Q variant (also known as c.3176G>A), located in coding exon 19 of the CCDC40 gene, results from a G to A substitution at nucleotide position 3176. The arginine at codon 1059 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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, |
RCV002483769 | SCV002793946 | uncertain significance | Primary ciliary dyskinesia 15 | 2021-07-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003411489 | SCV004113209 | uncertain significance | CCDC40-related condition | 2023-06-08 | criteria provided, single submitter | clinical testing | The CCDC40 c.3176G>A variant is predicted to result in the amino acid substitution p.Arg1059Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-78071198-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |