Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657969 | SCV000779740 | pathogenic | not provided | 2021-06-04 | criteria provided, single submitter | clinical testing | Published functional studies suggest a damaging effect; P243L variant causes shortening of neurites and that the P243 residue plays a role in the intradimer interaction of the tubulin proteins (Zheng et al., 2017); Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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: 32203252, 28835377, 27535533) |
Laboratory of Molecular Genetics |
RCV000657969 | SCV000920517 | likely pathogenic | not provided | 2018-08-08 | criteria provided, single submitter | clinical testing | |
Hudson |
RCV003303088 | SCV004009656 | uncertain significance | Complex cortical dysplasia with other brain malformations 5 | 2023-04-17 | criteria provided, single submitter | research | |
Invitae | RCV000657969 | SCV004641529 | uncertain significance | not provided | 2023-04-09 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TUBB2A protein function. ClinVar contains an entry for this variant (Variation ID: 546138). This missense change has been observed in individual(s) with clinical features of cortical malformation syndrome (PMID: 32203252). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 243 of the TUBB2A protein (p.Pro243Leu). |