Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV004556128 | SCV005045250 | uncertain significance | Complex cortical dysplasia with other brain malformations 7 | 2024-05-22 | criteria provided, single submitter | curation | The heterozygous p.Met299Val variant in TUBB2B was identified by our study in 4 family members with cortical dysplasia, complex, with other brain malformations 7. The variant has not been previously reported in individuals with cortical dysplasia, complex, with other brain malformations 7 and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The number of missense variants reported in TUBB2B in the general population is lower than expected, suggesting there is little benign variation in this gene and slightly increasing the possibility that a missense variant in this gene may not be tolerated. In summary, the clinical significance of the p.Met299Val variant is uncertain. ACMG/AMP Criteria applied: PP1, PM2_Supporting, PP3_Moderate, PP2 (Richards 2015). |