Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001233734 | SCV001406342 | uncertain significance | Immunodeficiency 14 | 2024-08-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 736 of the PIK3CD protein (p.Asp736Asn). This variant is present in population databases (rs547875116, gnomAD 0.006%). 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: 960245). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PIK3CD protein function with a negative 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. |
Revvity Omics, |
RCV003130207 | SCV003808372 | uncertain significance | not provided | 2019-11-18 | criteria provided, single submitter | clinical testing | |
Rarefied Biosciences Lab | RCV004801933 | SCV005421945 | likely benign | Activated PI3K-delta syndrome | no assertion criteria provided | research | p.Asp736Asn is classified here as likely benign due to experimental evidence show no gain of mTOR function in B or T cells. The proportion of transitional B cells is normal. The proportion of circulating TFH is high compared to healthy controls, but this finding is not unique to APDS. |