ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1634A>G (p.Glu545Gly)

dbSNP: rs121913274
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genomics Laboratory, Washington University in St. Louis RCV004562209 SCV005049522 pathogenic PIK3CA related overgrowth syndrome 2024-02-02 criteria provided, single submitter clinical testing A PIK3CA c.1634A>G (p.Glu545Gly) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in multiple individuals with PIK3CA-Related Overgrowth Spectrum (PROS) disorders (Luks VL et al., PMID: 25681199; Serio VB et al., PMID: 37662840; Vahidnezhad H et al., PMID: 27037860). The PIK3CA c.1634A>G (p.Glu545Gly) variant has been reported numerous times in the Catalogue of Somatic Mutations in Cancer (COSMIC) (Genomic Mutation ID: COSV55873220). This variant is absent from the general population (gnomAD v4.0.0), indicating it is not a common variant. Computational predictors indicate that this variant is damaging, evidence that correlates with impact to PIK3CA function. The PIK3CA gene is defined by the ClinGen Brain Malformations Variant Curation Expert Panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (Lai et al., PMID: 35997716). Other variants in the same codon, c.1634A>C (p.Glu545Ala), c.1633G>A (p.Glu545Lys), and c.1635G>T (p.Glu545Asp), have been reported and are considered pathogenic/likely pathogenic (ClinVar Variation IDs: 13659, 13655, and 217293). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868) and gene-specific practices from the ClinGen Criteria Specification Registry, the PIK3CA c.1634A>G (p.Glu545Gly) variant is classified as pathogenic.
OMIM RCV000014637 SCV000034892 pathogenic Carcinoma of colon 2007-08-14 no assertion criteria provided literature only
OMIM RCV000014638 SCV000034893 pathogenic Epidermal nevus 2007-08-14 no assertion criteria provided literature only

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