Submissions for variant NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)

dbSNP: rs1057519925

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Undiagnosed Diseases Network,NIH	RCV000991209	SCV001142587	pathogenic	Megalencephaly-capillary malformation-polymicrogyria syndrome	2019-05-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000991209	SCV001521015	pathogenic	Megalencephaly-capillary malformation-polymicrogyria syndrome	2020-06-25	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001526693	SCV001737114	pathogenic	CLOVES syndrome		criteria provided, single submitter	clinical testing
GeneDx	RCV001775789	SCV002013346	pathogenic	not provided	2021-05-17	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect: increased phosphorylation of AKT on serine 473 (Rudd et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23352210, 29759595, 21266528, 26619011, 21531001, 27834349, 27631024, 30063105, 27037860, 31263565)
Invitae	RCV001861479	SCV002247469	pathogenic	Cowden syndrome	2021-10-14	criteria provided, single submitter	clinical testing
Daryl Scott Lab,Baylor College of Medicine	RCV002244865	SCV002515365	pathogenic	PIK3CA-related disorder	2022-02-01	criteria provided, single submitter	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV001775789	SCV002525708	pathogenic	not provided	2021-08-26	criteria provided, single submitter	clinical testing	This variant has previously been reported in multiple unrelated individuals with a molecular diagnosis of PROS, including those with reported overgrowth and macrodactyly (PMID: 27631024, PMID: 31263565). The p.Glu453Lys variant substitutes the glutamic acid at position 453 with lysine within the C2 phosphatidylinositol 3-kinase domain of the PIK3CA protein (UniProt P42336, aa# 330-487). This is a recurrent hotspot. PIK3CA variants associated with PROS overlap those reported as oncogenic variants found in multiple tumor types (COSMIC and cBioPortal Databases)
Database of Curated Mutations (DoCM)	RCV000430361	SCV000506827	likely pathogenic	Squamous cell lung carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000440626	SCV000506828	likely pathogenic	Squamous cell carcinoma of the head and neck	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000422944	SCV000506829	likely pathogenic	Gastric adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000433137	SCV000506830	likely pathogenic	Lung adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000443243	SCV000506831	likely pathogenic	Malignant neoplasm of body of uterus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000423945	SCV000506832	likely pathogenic	Breast neoplasm	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000434215	SCV000506833	likely pathogenic	Neoplasm of brain	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000442682	SCV000506834	likely pathogenic	Hepatocellular carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000425038	SCV000506835	likely pathogenic	Glioblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000435327	SCV000506836	likely pathogenic	Transitional cell carcinoma of the bladder	2016-05-31	no assertion criteria provided	literature only
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785580	SCV000924154	likely pathogenic	Neoplasm of ovary	2018-12-01	no assertion criteria provided	research
MAGI's Lab - Research,MAGI Group	RCV001327961	SCV001437637	pathogenic	Abnormality of cardiovascular system morphology		no assertion criteria provided	provider interpretation