Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002404004 | SCV002711898 | uncertain significance | Inborn genetic diseases | 2022-10-01 | criteria provided, single submitter | clinical testing | The p.I593V variant (also known as c.1777A>G), located in coding exon 11 of the PIK3CA gene, results from an A to G substitution at nucleotide position 1777. The isoleucine at codon 593 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005097749 | SCV005734544 | uncertain significance | Cowden syndrome | 2024-08-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 593 of the PIK3CA protein (p.Ile593Val). This variant is present in population databases (rs200694869, gnomAD 0.006%). This missense change has been observed in individual(s) with PIK3CA-related conditions (PMID: 37486637). ClinVar contains an entry for this variant (Variation ID: 1779895). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PIK3CA 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. |