ClinVar Miner

Submissions for variant NM_017950.4(CCDC40):c.3176G>A (p.Arg1059Gln)

gnomAD frequency: 0.00019  dbSNP: rs200902434
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Total submissions: 4
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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, Fulgent Genetics RCV002483769 SCV002793946 uncertain significance Primary ciliary dyskinesia 15 2021-07-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences 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.

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