Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002272891 | SCV002557336 | pathogenic | Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures | 2022-09-02 | 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 Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (MIM#618088). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codons in this gene are known to escape nonsense-mediated decay (PMID 30057031; PMID 30166628) with at least 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other truncating variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (Decipher, PMID 30057031; PMID 30166628; PMID 31432588). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an individual. PMID 30166628 report this variant as heterozygous and de novo in a 48 year old female diagnosed with developmental regression in childhood, cerebellar dysmetria and epilepsy. (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Institute of Human Genetics, |
RCV002272891 | SCV004242430 | pathogenic | Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures | 2023-12-13 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1,PS2_MOD,PS4_MOD,PM2_SUP |