Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000414322 | SCV000492003 | uncertain significance | not specified | 2016-11-28 | criteria provided, single submitter | clinical testing | The E1010A variant in the PIK3CD gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E1010A variant was not observed at any significant frequency 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 E1010A variant 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 where amino acids with similar properties to Glutamic Acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E1010A as a variant of uncertain significance. |
Invitae | RCV000799093 | SCV000938742 | uncertain significance | Immunodeficiency 14 | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1010 of the PIK3CD protein (p.Glu1010Ala). This variant is present in population databases (rs142050444, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. ClinVar contains an entry for this variant (Variation ID: 373411). 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 PIK3CD 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. |