Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818088 | SCV000958683 | uncertain significance | Immunodeficiency 14 | 2024-01-14 | 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 186 of the PIK3CD protein (p.Pro186Leu). This variant is present in population databases (rs779715026, 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: 660809). 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 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. |
Ambry Genetics | RCV003279105 | SCV004004733 | uncertain significance | Inborn genetic diseases | 2023-06-02 | criteria provided, single submitter | clinical testing | The c.557C>T (p.P186L) alteration is located in exon 5 (coding exon 3) of the PIK3CD gene. This alteration results from a C to T substitution at nucleotide position 557, causing the proline (P) at amino acid position 186 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003892752 | SCV004712331 | uncertain significance | PIK3CD-related condition | 2024-01-11 | criteria provided, single submitter | clinical testing | The PIK3CD c.557C>T variant is predicted to result in the amino acid substitution p.Pro186Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |