Submissions for variant NM_006218.4(PIK3CA):c.1636C>A (p.Gln546Lys)

dbSNP: rs121913286

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical and Molecular Genetics, Hospital Universitario La Paz	RCV001705592	SCV001934210	pathogenic	Segmental undergrowth associated with mainly venous malformation with capillary component	2021-04-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001762046	SCV001990614	uncertain significance	not provided	2019-04-04	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Missense variants in nearby residues reported in the Human Gene Mutation Database in individuals with PIK3CA-related disorders (Stenson et al., 2014); Has not been previously published in association with PIK3CA-related neurodevelopmental disorders to our knowledge; This variant is associated with the following publications: (PMID: 16930767, 19272638, 19394761, 18221484, 26339434, 31536475, 30591517, 25681199, 27307077, 28453743, 29786783, 29985963)
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV001762046	SCV002525576	pathogenic	not provided	2021-12-28	criteria provided, single submitter	clinical testing	This variant has previously been reported in multiple unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 32350708 and others). The p.Gln546Lys variant substitutes the glutamate at position 546 with lysine within the PIK helical domain of the PIK3CA protein (UniProt P42336). This is an activating mutation that results in ligand-independent activation of the PI3K-AKT-mTOR pathway and increased proliferation in vitro (PMID: 26627007).
Genetics and Personalized Medicine Clinic, Tartu University Hospital	RCV004698784	SCV005199859	pathogenic	Megalencephaly-capillary malformation-polymicrogyria syndrome		criteria provided, single submitter	clinical testing
OMIM	RCV000014639	SCV000034894	pathogenic	OVARIAN CANCER, EPITHELIAL, SOMATIC	2004-11-01	no assertion criteria provided	literature only
OMIM	RCV000014640	SCV000034895	pathogenic	Carcinoma of colon	2004-11-01	no assertion criteria provided	literature only
Clinical Genomics Laboratory, Washington University in St. Louis	RCV000201230	SCV000255987	likely pathogenic	PIK3CA related overgrowth syndrome	2014-12-01	no assertion criteria provided	clinical testing
Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere	RCV000205164	SCV000259003	likely pathogenic	Malignant tumor of prostate		no assertion criteria provided	research
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000436582	SCV000924153	pathogenic	Ovarian neoplasm	2018-12-01	no assertion criteria provided	research