Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV000767481 | SCV000898096 | pathogenic | Tubulinopathy | 2018-07-01 | criteria provided, single submitter | literature only | A variant that is classified as pathogenic has been identified in the TUBA1A gene in a 10 years old born individual of male sex. The c.1225G>A, p.(Val409Ile) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Bahi-Buisson et al. Brain, 2014 PMID: 24860126. HPO-standardized clinical features were: Dysplastic corpus callosum (HP:0006989); Pachygyria (HP:0001302); no Abnormal cerebellum morphology (-HP:0001317); Microcephaly (HP:0000252) |
| Gene |
RCV001547766 | SCV001767548 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | 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 does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31574570, 33064843, 25140959, 24860126) |
| Invitae | RCV001547766 | SCV004295045 | uncertain significance | not provided | 2022-12-08 | 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. This variant disrupts the p.Val409 amino acid residue in TUBA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24860126). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 not expected to disrupt TUBA1A protein function. ClinVar contains an entry for this variant (Variation ID: 625504). This missense change has been observed in individual(s) with tubulin-related cortical malformations (PMID: 24860126, 25140959). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 409 of the TUBA1A protein (p.Val409Ile). |