ClinVar Miner

Submissions for variant NM_001366385.1(CARD14):c.1799C>T (p.Pro600Leu)

gnomAD frequency: 0.00001  dbSNP: rs746260783
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478014 SCV000569162 uncertain significance not provided 2016-01-26 criteria provided, single submitter clinical testing The P600L variant in the CARD14 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P600L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P600L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P600L as a variant of uncertain significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263697 SCV002543240 uncertain significance Autoinflammatory syndrome 2016-12-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003766678 SCV004571946 uncertain significance Pityriasis rubra pilaris; Psoriasis 2 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 600 of the CARD14 protein (p.Pro600Leu). This variant is present in population databases (rs746260783, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. ClinVar contains an entry for this variant (Variation ID: 420354). 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 expected to disrupt CARD14 protein function with a positive predictive value of 80%. 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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