Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000624048 | SCV000741838 | likely pathogenic | Inborn genetic diseases | 2016-11-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000509989 | SCV001571660 | pathogenic | Epileptic encephalopathy, infantile or early childhood, 1 | 2021-01-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002269282 | SCV002552746 | pathogenic | not provided | 2022-03-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11461966, 20700442, 10473536, 25262651, 27597899, 8052858, 15800199, 25245802, 3029762, 24140049, 22015374, 10627609, 28942967, 33963760) |
| MGZ Medical Genetics Center | RCV000509989 | SCV002581862 | pathogenic | Epileptic encephalopathy, infantile or early childhood, 1 | 2022-08-25 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV000509989 | SCV002767479 | pathogenic | Epileptic encephalopathy, infantile or early childhood, 1 | 2022-03-31 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 91 (MIM#617711), and arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development (MIM#618265), respectively (PMIDs: 32593294, 29432562). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0600 - Variant is located in the annotated protein phosphatase 2B (PP2B) catalytic domain (PMID: 28942967). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported as de novo in multiple affected individuals (PMIDs: 28942967, 33963760). (SP) 1010 - Functional evidence for this variant is inconclusive. Overexpression studies using yeast showed the mutant maintained tolerance to growth condition with high extracellular Ca2+, similar to wild-type (PMID: 29432562). (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Unidad de Genómica Garrahan, |
RCV003483646 | SCV004232388 | pathogenic | Epileptic encephalopathy | 2024-01-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002269282 | SCV004293207 | pathogenic | not provided | 2023-09-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 282 of the PPP3CA protein (p.Glu282Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PPP3CA-related conditions (PMID: 28942967). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 441275). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PPP3CA protein function. |
| Molecular Genetics Lab, |
RCV003883152 | SCV004697645 | pathogenic | Epileptic encephalopathy, infantile or early childhood, 1; Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development | criteria provided, single submitter | clinical testing | ||
| OMIM | RCV000509989 | SCV000607751 | pathogenic | Epileptic encephalopathy, infantile or early childhood, 1 | 2021-03-15 | no assertion criteria provided | literature only |