ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1489A>C (p.Asn497His)

gnomAD frequency: 0.00001  dbSNP: rs199563773
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000631219 SCV000752233 uncertain significance Cowden syndrome 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 497 of the PIK3CA protein (p.Asn497His). This variant is present in population databases (rs199563773, gnomAD 0.003%). 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: 526640). 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.
Mendelics RCV000708944 SCV000838052 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002388001 SCV002701655 uncertain significance Inborn genetic diseases 2023-07-27 criteria provided, single submitter clinical testing The p.N497H variant (also known as c.1489A>C), located in coding exon 8 of the PIK3CA gene, results from an A to C substitution at nucleotide position 1489. The asparagine at codon 497 is replaced by histidine, an amino acid with 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.

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