Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001909931 | SCV002178679 | uncertain significance | Cowden syndrome | 2021-06-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PIK3CA-related conditions. This variant is present in population databases (rs745847400, ExAC 0.02%). This sequence change replaces threonine with isoleucine at codon 435 of the PIK3CA protein (p.Thr435Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 PIK3CA protein function. |
| Ambry Genetics | RCV002386709 | SCV002691212 | uncertain significance | Inborn genetic diseases | 2022-09-26 | criteria provided, single submitter | clinical testing | The p.T435I variant (also known as c.1304C>T), located in coding exon 7 of the PIK3CA gene, results from a C to T substitution at nucleotide position 1304. The threonine at codon 435 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |