Total submissions: 32
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001836714 | SCV001949964 | pathogenic | Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | 2022-02-12 | reviewed by expert panel | curation | The c.1624G>A (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.Glu542Lys). Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PS2_Moderate; PMID: 22658544). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_VS; PMIDs: 25722288, 25681199, 22658544, 29446767, 26851524, 25292196, 23100325; identified in 1 individual with neuroimaging demonstrating at least one large cerebral hemisphere with cortical malformation, at least 6 individuals with a clinical diagnosis of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome; (MPPH) or megalencephaly-capillary malformation-polymicrogyria syndrome; (MCAP), at least 9 individuals with segmental overgrowth or vascular malformation of a limb or region of the body, and at least 9 tumor samples in the literature and COSMIC). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). PIK3CA, in which the variant was identified, is defined by the ClinGen Brain Malformations 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 (PP2). In summary, this variant meets the criteria to be classified as Pathogenic for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: PS2_M, PS4_VS, PM2_P, PP2; 12 points (VCEP specifications version 1; Approved: 1/31/2021) |
Gene |
RCV000416776 | SCV001830827 | pathogenic | not provided | 2021-01-22 | 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; This variant is associated with the following publications: (PMID: 25599672, 24374682, 23100325, 25044986, 22357840, 22658544, 23066039, 26851524, 27631024, 29446767) |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV000416776 | SCV002525701 | pathogenic | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | This variant has previously been reported in several unrelated individuals with PIK3CA-related segmental overgrowth syndrome (PMID: 31536475, PMID: 25681199, PMID: 29985963 and others). The p.E542K variant substitutes the glutamic acid at position 542 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). |
OMIM | RCV000024622 | SCV000050488 | pathogenic | CLOVES syndrome | 2012-06-08 | no assertion criteria provided | literature only | |
Gene |
RCV000024622 | SCV000086942 | pathologic | CLOVES syndrome | 2013-08-15 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Laboratory for Molecular Medicine, |
RCV000151649 | SCV000199901 | pathogenic | Neoplasm of ovary | 2011-10-12 | no assertion criteria provided | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000154513 | SCV000204184 | pathogenic | Non-small cell lung carcinoma | 2011-10-12 | no assertion criteria provided | clinical testing | |
Department of Medical Genetics, |
RCV000416776 | SCV000258982 | pathogenic | not provided | 2015-09-01 | no assertion criteria provided | case-control | |
Database of Curated Mutations |
RCV000154513 | SCV000503916 | pathogenic | Non-small cell lung carcinoma | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421639 | SCV000503917 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431872 | SCV000503918 | pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442348 | SCV000503919 | pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000151649 | SCV000503920 | pathogenic | Neoplasm of ovary | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433007 | SCV000503921 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000445059 | SCV000503922 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425548 | SCV000503923 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435811 | SCV000503924 | likely pathogenic | Papillary renal cell carcinoma, sporadic | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419905 | SCV000503925 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426691 | SCV000503926 | likely pathogenic | Prostate adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436932 | SCV000503927 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419440 | SCV000503928 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431000 | SCV000503929 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441707 | SCV000503930 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420078 | SCV000503931 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430763 | SCV000503932 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438815 | SCV000503933 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
OMIM | RCV000709693 | SCV000839593 | pathogenic | CLAPO syndrome | 2012-06-08 | no assertion criteria provided | literature only | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000151649 | SCV000923935 | pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research | |
Institute of Medical Sciences, |
RCV001255687 | SCV001432252 | pathogenic | Lip and oral cavity carcinoma | 2019-04-30 | no assertion criteria provided | research | |
MAGI's Lab - |
RCV001327962 | SCV001437638 | pathogenic | Abnormality of cardiovascular system morphology | no assertion criteria provided | provider interpretation | ||
James Bennett Lab, |
RCV001730477 | SCV001960169 | pathogenic | Cerebrofacial Vascular Metameric Syndrome (CVMS) | 2021-09-30 | no assertion criteria provided | clinical testing | |
OMIM | RCV001728093 | SCV001976537 | pathogenic | CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC | 2012-06-08 | no assertion criteria provided | literature only |