ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1749G>A (p.Met583Ile)

gnomAD frequency: 0.00001  dbSNP: rs1302992156
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001295117 SCV001484029 uncertain significance Cowden syndrome 2020-07-20 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PIK3CA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 583 of the PIK3CA protein (p.Met583Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine.
Ambry Genetics RCV002411937 SCV002716114 uncertain significance Inborn genetic diseases 2021-09-04 criteria provided, single submitter clinical testing The p.M583I variant (also known as c.1749G>A), located in coding exon 11 of the PIK3CA gene, results from a G to A substitution at nucleotide position 1749. The methionine at codon 583 is replaced by isoleucine, an amino acid with highly 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.

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