ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1130C>G (p.Pro377Arg)

gnomAD frequency: 0.00009  dbSNP: rs113613074
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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 RCV000461259 SCV000541312 uncertain significance Cowden syndrome 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 377 of the PIK3CA protein (p.Pro377Arg). This variant is present in population databases (rs113613074, gnomAD 0.02%). 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: 403909). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PIK3CA protein function with a positive predictive value of 95%. 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 RCV000764479 SCV000895550 uncertain significance Familial cancer of breast; Megalencephaly-capillary malformation-polymicrogyria syndrome; Lung carcinoma; Congenital macrodactylia; Seborrheic keratosis; Epidermal nevus; Ovarian neoplasm; CLAPO syndrome; CLOVES syndrome; Carcinoma of colon; Neoplasm of stomach; Cowden syndrome 5; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004533141 SCV004117348 uncertain significance PIK3CA-related disorder 2022-11-23 criteria provided, single submitter clinical testing The PIK3CA c.1130C>G variant is predicted to result in the amino acid substitution p.Pro377Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-178922361-C-G). 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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