Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486919 | SCV000571615 | uncertain significance | not provided | 2016-09-15 | criteria provided, single submitter | clinical testing | To our knowledge, the E808K variant in the CARD14 gene has not been reported previously as a pathogenic variant, nor as a benign variant. It was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. E808K is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, we interpret E808K as a variant of uncertain significance. |
Labcorp Genetics |
RCV002526625 | SCV003447132 | uncertain significance | Pityriasis rubra pilaris; Psoriasis 2 | 2022-11-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 422207). 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. 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 CARD14 protein function. This variant has not been reported in the literature in individuals affected with CARD14-related conditions. This variant is present in population databases (rs759612018, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 808 of the CARD14 protein (p.Glu808Lys). |