ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1304C>T (p.Thr435Ile)

gnomAD frequency: 0.00001  dbSNP: rs745847400
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001909931 SCV002178679 uncertain significance Cowden syndrome 2021-06-19 criteria provided, single submitter clinical testing 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. 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.
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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.