Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV000767413 | SCV000898028 | 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 18 months old born individual of male sex. The c.629A>G, p.(Tyr210Cys) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Jansen et al. Neurology, 2011 PMID: 21403111. HPO-standardized clinical features were: Hypoplasia of the corpus callosum (HP:0002079); Agyria-pachygyria (HP:0031883, HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); Hypoplasia of the brainstem (HP:0002365); Dilated fourth ventricle (HP:0002198); Abnormality of the internal capsule (HP:0012502); Congenital microcephaly (HP:0011451); Microcephaly (HP:0000252); Spasticity (HP:0001257); Focal seizures (HP:0007359) |
| Invitae | RCV001388958 | SCV001590144 | pathogenic | not provided | 2022-10-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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 TUBA1A protein function. ClinVar contains an entry for this variant (Variation ID: 625474). This missense change has been observed in individual(s) with lissencephaly (PMID: 21403111). In at least one individual the variant was observed to be de novo. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 210 of the TUBA1A protein (p.Tyr210Cys). |
| Gene |
RCV001388958 | SCV004025495 | pathogenic | not provided | 2023-08-10 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 21403111, 26493046, 28412269, 22264709, 30744660, 35892608) |