Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000578189 | SCV000680024 | pathogenic | Developmental and epileptic encephalopathy, 11 | 2023-07-16 | 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. Variants causing a gain of function result in developmental and epileptic encephalopathy 11 (MIM#613721) or benign familial infantile seizures 3 (MIM#607745), whereas variants causing loss of function result in autism spectrum disorder and/or intellectual disability, with or without childhood-onset seizures (OMIM, PMIDs: 29691040, 31904126). 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to aspartic acid. (I) 0219 - This variant is non-coding in an alternative transcript. However, it is coding in the neonatal isoform, which gradually gets replaced by the adult isoform post-development (PMID: 23935176). (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ion transport protein (NCBI). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been regarded as pathogenic in ClinVar and was reported as de novo in at least two unrelated cases with early-infantile severe epilepsy (ClinVar, PMID: 23935176). (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by segregation analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Equipe Genetique des Anomalies du Developpement, |
RCV000578189 | SCV000966183 | pathogenic | Developmental and epileptic encephalopathy, 11 | 2018-08-28 | criteria provided, single submitter | clinical testing |