Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000767425 | SCV000898040 | 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 2 years old born individual of male sex. The c.74G>T, p.(Cys25Phe) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Yokoi et al. Sci Rep, 2015 PMID: 26493046. HPO-standardized clinical features were: Agenesis of the corpus callosum (HP:0001274); Agyria-pachygyria (HP:0031883, HP:0001302); Cerebellar vermis hypoplasia (HP:0001320); no Abnormality of brainstem morphology (-HP:0002363); Dilation of lateral ventricles (HP:0006956); no Congenital microcephaly (-HP:0011451); Spasticity (HP:0001257); Infantile spasms (HP:0012469) |
Invitae | RCV003558566 | SCV004295048 | pathogenic | not provided | 2022-12-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TUBA1A function (PMID: 26493046). 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: 625481). This missense change has been observed in individual(s) with lissencephaly (PMID: 26493046). 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 cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 25 of the TUBA1A protein (p.Cys25Phe). |