ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1476T>G (p.Ile492Met)

dbSNP: rs557949672
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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 RCV001240400 SCV001413338 uncertain significance Cowden syndrome 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 492 of the PIK3CA protein (p.Ile492Met). This variant is present in population databases (rs557949672, gnomAD 0.009%). 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: 965858). 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.
Fulgent Genetics, Fulgent Genetics RCV005029818 SCV005661903 uncertain significance Familial cancer of breast; Hemifacial myohyperplasia; Megalencephaly-capillary malformation-polymicrogyria syndrome; Congenital macrodactylia; Seborrheic keratosis; Epidermal nevus; CLAPO syndrome; CLOVES syndrome; Ovarian cancer; Cerebral cavernous malformation 4; Cowden syndrome 5; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Lung cancer 2024-04-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004738213 SCV005359684 uncertain significance PIK3CA-related disorder 2024-04-12 no assertion criteria provided clinical testing The PIK3CA c.1476T>G variant is predicted to result in the amino acid substitution p.Ile492Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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