ClinVar Miner

Submissions for variant NM_017950.4(CCDC40):c.1480C>T (p.Arg494Cys)

dbSNP: rs200858130
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000602013 SCV000711286 uncertain significance not specified 2016-07-13 criteria provided, single submitter clinical testing The p.Arg494Cys variant in CCDC40 has not been previously reported in individual s with pulmonary disease, but has been identified in 1/65244 European chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs200858130). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg494Cys variant is uncertain.
Invitae RCV002532739 SCV003307057 uncertain significance Primary ciliary dyskinesia 2022-01-28 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 504722). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. This variant is present in population databases (rs200858130, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 494 of the CCDC40 protein (p.Arg494Cys). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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