ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.1132T>C (p.Cys378Arg)

dbSNP: rs1724507777
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526537 SCV001736959 pathogenic CLOVES syndrome criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV003225150 SCV003921863 pathogenic Megalencephaly-capillary malformation-polymicrogyria syndrome criteria provided, single submitter clinical testing - Variant is absent from gnomAD (both v2 and v3). - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. - Another missense variant comparable to the one identified in this case has previous evidence of pathogenicity. The p.(Cys378Tyr) variant is recurrent in individuals with PIK3CA-related overgrowth spectrum disorders (ClinVar, PMID: 22729224, 28502725, 31585106). - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with PIK3CA-related overgrowth spectrum disorders (ClinVar, PMID: 33105631, 28502725, 30270358, 31585106). This variant was somatic mosaic in all reports where data was provided. - This variant has been shown to be de novo in the proband (parental status confirmed; by trio analysis). Additional information: - Gain of function is a known mechanism of disease in this gene and is associated with PIK3CA-related overgrowth disorders (various MIM#s; PMID: 30197175). - This gene is associated with autosomal dominant disease. - Variant is predicted to result in a missense amino acid change from cysteine to arginine. - This variant is confirmed somatic, with a variant allele frequency (VAF) of ~21% in the sample tested. - Variant is located in the annotated PI3K_C2 domain (Pfam). - No published segregation evidence has been identified for this variant.
MAGI's Lab - Research, MAGI Group RCV001265073 SCV001250711 likely pathogenic Klippel-Trénaunay syndrome no assertion criteria provided clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV003485684 SCV004240775 pathogenic Capillary malformation no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.