ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1528C>A (p.His510Asn)

gnomAD frequency: 0.00005  dbSNP: rs199747934
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547757 SCV000626807 uncertain significance Cowden syndrome 2023-09-18 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 510 of the PIK3CA protein (p.His510Asn). This variant is present in population databases (rs199747934, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. ClinVar contains an entry for this variant (Variation ID: 456529). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237894 SCV002009611 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis RCV003458454 SCV004177159 uncertain significance PIK3CA-Related Disorders 2023-08-07 criteria provided, single submitter clinical testing The PIK3CA c.1528C>A (p.His510Asn) variant was identified at a near heterozygous allelic fraction. This variant has been reported in the ClinVar database as a variant of uncertain significance by two submitters (ClinVar Variation ID:456529), and it has been reported in one case in the cancer database COSMIC (COSMIC Mutation ID: COSV55977943). The PIK3CA c.1528C>A (p.His510Asn) variant is only observed on 8/152164 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are conflicting as to the impact of this variant on the PIK3CA function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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.