Total submissions: 62
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001836707 | SCV001949970 | pathogenic | Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | 2022-02-11 | reviewed by expert panel | curation | The c.3140A>G (NM_006218.4) variant in PIK3CA is a missense variant predicted to cause substitution of (p.His1047Arg). This variant is present in one individual in gnomAD v2.1.1 (PM2_Supporting). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_VS; PMIDs: 27191687, 28328134, 25292196, 22729222, 25424831, 465 entries in COSMIC, Segmental overgrowth or vascular malformation of a limb or region of the body, present in patient derived cell lines). 60 independent Ba/F3 and 57 independent MCF10A experiments showed this variant has a proliferative effect indicating that this variant impacts protein function (PMID:29533785 ) (PS3_Moderate). This variant resides within the kinase domain of PIK3CA that is defined as a critical functional domain by the ClinGen BMEP (PMIDs: 26637981, 24459181, 27631024) (PM1_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). Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PS2_Moderate; PMID: 25424831). 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: PM2_P, PS4_VS, PS3_M, PM1_P, PP2, PS2_M; 15 points (VCEP specifications version 1; Approved: 1/31/2021) |
Donald Williams Parsons Laboratory, |
RCV000487449 | SCV000292259 | pathogenic | Rosette-forming glioneuronal tumor | criteria provided, single submitter | clinical testing | ||
Equipe Genetique des Anomalies du Developpement, |
RCV000024621 | SCV000803841 | pathogenic | CLOVES syndrome | criteria provided, single submitter | clinical testing | ||
Biesecker Lab Rare Disease, |
RCV000201231 | SCV000898478 | pathogenic | PIK3CA related overgrowth syndrome | 2019-04-19 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001092442 | SCV001248958 | pathogenic | not provided | 2021-06-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000024621 | SCV001428754 | pathogenic | CLOVES syndrome | 2019-11-11 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001092442 | SCV001446687 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Equipe Genetique des Anomalies du Developpement, |
RCV001526648 | SCV001737079 | pathogenic | Congenital macrodactylia | criteria provided, single submitter | clinical testing | ||
Institute of Medical and Molecular Genetics, |
RCV001705590 | SCV001934209 | pathogenic | Segmental undergrowth associated with lymphatic malformation | 2021-04-06 | criteria provided, single submitter | clinical testing | |
Institute of Medical and Molecular Genetics, |
RCV001705589 | SCV001934211 | pathogenic | Segmental undergrowth associated with mainly venous malformation with capillary component | 2021-04-06 | criteria provided, single submitter | clinical testing | |
Laboratory of Medical Genetics, |
RCV001729349 | SCV001976965 | pathogenic | CLAPO syndrome | 2021-10-01 | criteria provided, single submitter | clinical testing | PS3, PM1, PM2, PM5, PP2, PP3, PP4, PP5 |
Institute for Clinical Genetics, |
RCV001092442 | SCV002009609 | likely pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV001807727 | SCV002059601 | pathogenic | Megalencephaly-capillary malformation-polymicrogyria syndrome | 2021-02-12 | criteria provided, single submitter | clinical testing | |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV001092442 | SCV002061476 | pathogenic | not provided | 2021-08-05 | criteria provided, single submitter | clinical testing | PS4, PS3, PM2 |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV001092442 | SCV002525705 | pathogenic | not provided | 2020-09-20 | criteria provided, single submitter | clinical testing | This variant substitutes the histidine with arginine at position 1047 within the PIK3CA kinase domain. This is a recurrent pathogenic variant. Several unrelated individuals with PIK3CA-related segmental overgrowth syndrome due to the somatic activating PIK3CA p.His1047Arg variant have previously been reported (PMID: 25681199, PMID: 26637981, PMID: 24903541, PMID: 30180809, PMID: 28328134 and others). |
Gene |
RCV001092442 | SCV002559314 | pathogenic | not provided | 2022-08-03 | criteria provided, single submitter | clinical testing | Reported as a somatic variant in various tumor samples (Campbell et al., 2004; Li et al., 2005); Published functional studies demonstrate increased lipid kinase activity and transforming activities, and a mouse model with this variant demonstrated increased body weight, increased organ size, and severe metabolic defects (Ikenoue et al., 2005; Kinross et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16322209, 15289301, 15016963, 25599672, 23100325, 25550458, 15930273, 16432179, 19805105, 21708979, 15520168, 15784156, 27631024, 24903541, 22658544, 32770747, 34568242, 34075207) |
Oxford Medical Genetics Laboratories, |
RCV003325939 | SCV003853395 | pathogenic | Klippel-Trenaunay-like-Syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000014622 | SCV000034877 | pathogenic | Breast adenocarcinoma | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000014623 | SCV000034878 | pathogenic | OVARIAN CANCER, EPITHELIAL, SOMATIC | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000014624 | SCV000034879 | pathogenic | Carcinoma of colon | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV002508124 | SCV000034880 | pathogenic | Gastric cancer | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000014626 | SCV000034881 | pathogenic | Hepatocellular carcinoma | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000014627 | SCV000034882 | pathogenic | Non-small cell lung carcinoma | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000014628 | SCV000034883 | pathogenic | Seborrheic keratosis | 2012-06-24 | no assertion criteria provided | literature only | |
OMIM | RCV000024621 | SCV000050487 | pathogenic | CLOVES syndrome | 2012-06-24 | no assertion criteria provided | literature only | |
Gene |
RCV000024621 | SCV000086944 | not provided | CLOVES syndrome | no assertion provided | literature only | ||
Laboratory for Molecular Medicine, |
RCV000014627 | SCV000199905 | pathogenic | Non-small cell lung carcinoma | 2010-08-05 | no assertion criteria provided | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000154516 | SCV000204187 | pathogenic | Neoplasm of ovary | 2010-08-05 | no assertion criteria provided | clinical testing | |
Clinical Genomics Laboratory, |
RCV000201231 | SCV000255984 | pathogenic | PIK3CA related overgrowth syndrome | 2015-04-01 | no assertion criteria provided | clinical testing | |
Database of Curated Mutations |
RCV000432506 | SCV000504107 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442164 | SCV000504108 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425956 | SCV000504109 | likely pathogenic | Uterine carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436234 | SCV000504110 | pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000014627 | SCV000504111 | pathogenic | Non-small cell lung carcinoma | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426498 | SCV000504112 | likely pathogenic | Brainstem glioma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437153 | SCV000504113 | pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419938 | SCV000504114 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430589 | SCV000504115 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437782 | SCV000504116 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420562 | SCV000504117 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431232 | SCV000504118 | likely pathogenic | Adrenal cortex carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438435 | SCV000504119 | likely pathogenic | Neoplasm | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000154516 | SCV000504120 | pathogenic | Neoplasm of ovary | 2014-10-02 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428372 | SCV000504121 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000014626 | SCV000504122 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421855 | SCV000504123 | likely pathogenic | Medulloblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432543 | SCV000504124 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442736 | SCV000504125 | likely pathogenic | Prostate adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422442 | SCV000504126 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433127 | SCV000504127 | likely pathogenic | Papillary renal cell carcinoma type 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443546 | SCV000504128 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426614 | SCV000504129 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437287 | SCV000504130 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442731 | SCV000504131 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
OMIM | RCV000709691 | SCV000839591 | pathogenic | MACRODACTYLY, SOMATIC | 2012-06-24 | no assertion criteria provided | literature only | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000154516 | SCV000923968 | pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research | |
Institute of Medical Sciences, |
RCV001255686 | SCV001432251 | pathogenic | Lip and oral cavity carcinoma | 2019-04-30 | no assertion criteria provided | research | |
MAGI's Lab - |
RCV001327968 | SCV001437644 | pathogenic | Abnormal cardiovascular system morphology | no assertion criteria provided | provider interpretation | ||
James Bennett Lab, |
RCV001730472 | SCV001960168 | pathogenic | Cerebrofacial Vascular Metameric Syndrome (CVMS) | 2021-09-30 | no assertion criteria provided | clinical testing | |
OMIM | RCV001728091 | SCV001976535 | pathogenic | CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC | 2012-06-24 | no assertion criteria provided | literature only | |
Clinical Genetics Laboratory, |
RCV000024621 | SCV002583480 | pathogenic | CLOVES syndrome | 2022-06-02 | no assertion criteria provided | clinical testing | |
Medical Oncology, |
RCV003128082 | SCV003803732 | pathogenic | Breast carcinoma | no assertion criteria provided | clinical testing |