Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Equipe Genetique des Anomalies du Developpement, |
RCV001526537 | SCV001736959 | pathogenic | CLOVES syndrome | criteria provided, single submitter | clinical testing | ||
Victorian Clinical Genetics Services, |
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 - |
RCV001265073 | SCV001250711 | likely pathogenic | Klippel-Trénaunay syndrome | no assertion criteria provided | clinical testing | ||
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV003485684 | SCV004240775 | pathogenic | Capillary malformation | no assertion criteria provided | clinical testing |