Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute Of Human Genetics Munich, |
RCV000578289 | SCV000680418 | pathogenic | Lissencephaly due to TUBA1A mutation | 2017-11-16 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000767476 | SCV000898091 | 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 3 years old born individual of female sex. The c.1169G>A, p.(Arg390His) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Zanni et al. Eur J Pediatr Neurol, 2013 PMID: 23317684. HPO-standardized clinical features were: Partial agenesis of the corpus callosum, Hypoplasia of the corpus callosum (HP:0001338, HP:0002079); Perisylvian polymicrogyria (HP:0012650); Dysgenesis of the cerebellar vermis (HP:0002195); Hypoplasia of the brainstem (HP:0002365); Cerebellar dysplasia (HP:0007033); no Abnormal morphology of the hippocampus (HP:0025100); Dilation of lateral ventricles (HP:0006956); Abnormality of the internal capsule (HP:0012502); no Congenital microcephaly (-HP:0011451); no Microcephaly (-HP:0000252); Spasticity (HP:0001257); Strabismus (HP:0000486) |
| Gene |
RCV001562806 | SCV001785633 | pathogenic | not provided | 2021-12-07 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23317684, 28677066, 30744660, 33649541) |
| Baylor Genetics | RCV000578289 | SCV004183479 | pathogenic | Lissencephaly due to TUBA1A mutation | 2023-11-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001562806 | SCV004295046 | pathogenic | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg390 amino acid residue in TUBA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20466733, 22948023, 34246755). 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: 488628). This missense change has been observed in individual(s) with cortical malformation (PMID: 23317684, 28677066). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 390 of the TUBA1A protein (p.Arg390His). |
| Center for Genomic Medicine, |
RCV000578289 | SCV004804935 | pathogenic | Lissencephaly due to TUBA1A mutation | 2024-03-17 | criteria provided, single submitter | research | |
| Genome Diagnostics Laboratory, |
RCV000578289 | SCV000745684 | pathogenic | Lissencephaly due to TUBA1A mutation | 2015-05-01 | no assertion criteria provided | clinical testing | |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001562806 | SCV001953713 | pathogenic | not provided | no assertion criteria provided | clinical testing |