Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV004555154 | SCV005044067 | likely pathogenic | Complex cortical dysplasia with other brain malformations 7 | 2023-02-06 | criteria provided, single submitter | clinical testing | The de novo heterozygous c.845G>C p.(Arg282Pro) missense variant identified in the TUBB2B gene has not been reported in affected individuals in the literature. The variant is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.1739A>C variant is located in the last exon of this 4-exon gene and is predicted to replace a highly conserved arginine residue with proline at position 282 within the Tubulin C-terminal domain of the encoded protein [PMID: 32656949]. In silico predictions are in favor of the variant’s damaging effect [REVEL = 0.904]; however, functional studies to support or refute these predictions have not been reported. Based on the available evidence, de novo heterozygous c.845G>C p.(Arg282Pro) missense variant identified in the TUBB2B gene is reported as Likely Pathogenic. |