Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000147856 | SCV000195330 | uncertain significance | Complex cortical dysplasia with other brain malformations 1 | 2014-04-18 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000764099 | SCV000895063 | uncertain significance | Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement; Complex cortical dysplasia with other brain malformations 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Genetics Institute, |
RCV000147856 | SCV001593198 | likely pathogenic | Complex cortical dysplasia with other brain malformations 1 | 2021-05-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001550956 | SCV001771366 | pathogenic | not provided | 2021-11-05 | criteria provided, single submitter | clinical testing | Observed previously in a deceased fetus with a complex brain malformation and dysmorphic features and was inherited from a mother with abnormal brain imaging (Reches et al., 2018); Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); 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: 32169460, 30108342, 20829227) |
| Victorian Clinical Genetics Services, |
RCV000147856 | SCV005086573 | likely pathogenic | Complex cortical dysplasia with other brain malformations 1 | 2023-12-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0104 - Dominant negative is a known mechanism of disease in this gene and is associated with cortical dysplasia, complex, with other brain malformations 1 (MIM#614039) and fibrosis of extraocular muscles, congenital, 3A (MIM#600638) (PMID: 31219644). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (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 uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Pro243Arg) has been classified as likely pathogenic in ClinVar. (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic or likely pathogenic by multiple clinical laboratories in ClinVar, and also has two older VUS classifications. This variant has also been observed in a mother and her fetus, as well as another unrelated individual with TUBB3-related symptoms (PMID: 30108342, 31269740). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. This variant causes reduced neuronal gene expression in C. elegans. (PMID:26441521). (SP) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |