Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004594722 | SCV005086170 | pathogenic | Developmental and epileptic encephalopathy, 7 | 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 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 7 (DEE; MIM#613720) and benign neonatal seizures, 1 (BFNS; MIM#121200), respectively (PMID: 20437616). There is currently no phenotypic correlation in terms of variant types or protein location (PMID: 31418850). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance, however, this is only reported for patients with BFNS (PMID: 25959266). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to threonine (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional pore domain (PMID: 33333793). (SP) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. The variants p.(Pro285Leu) and p.(Pro285Ser) have been reported as likely pathogenic and pathogenic in ClinVar. (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as de novo in an individual with onset of seizures on day 2 of life, thin corpus callosum and severe developmental delay/intellectual disability (PMID: 31199083). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed; by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |