Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001004655 | SCV002768046 | pathogenic | Developmental and epileptic encephalopathy, 84 | 2021-05-06 | 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: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with developmental and epileptic encephalopathy 84 (MIM#618792). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (18 heterozygotes, 0 homozygotes). (SP) 0703 - Two other NMD predicted variants comparable to the one identified in this case have moderate previous evidence for pathogenicity (ClinVar, PMID: 32001716). (SP) 0803 - This variant has limited previous evidence of pathogenicity in two unrelated individuals with developmental epileptic encephalopathy (PMID: 32001716). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1001 - This variant has strong functional evidence supporting abnormal protein function. Patient derived fibroblast cells with p.R65*/p.Y367C showed dramatically reduced endogenous protein level. Cerebral organoid developed in vitro with the same genotype showed smaller and rougher edges compared to WT (PMID: 32001716). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Section for Clinical Neurogenetics, |
RCV000999489 | SCV001156130 | likely pathogenic | Epileptic encephalopathy | 2019-10-01 | no assertion criteria provided | research | |
OMIM | RCV001004655 | SCV001164103 | pathogenic | Developmental and epileptic encephalopathy, 84 | 2020-10-07 | no assertion criteria provided | literature only |