Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001266910 | SCV001445090 | likely pathogenic | Inborn genetic diseases | 2020-03-19 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change: The c.191G>A (p.R64Q) alteration is located in coding exon 2 of the TUBA1A gene. This alteration results from a G to A substitution at nucleotide position 191, causing the arginine (R) at amino acid position 64 to be replaced by a glutamine (Q). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the TUBA1A c.191G>A alteration was not observed, with coverage at this position. Alterations at the same codon have been observed in affected individuals: The Deciphering Developmental Disorders (DDD) database (https://decipher.sanger.ac.uk/) reported a single individual with a de novo c.191G>A (p.R64Q) alteration in TUBA1A. The patient was reported to have moderate intellectual disability. Another alteration affecting the same codon, p.R64W, was de novo in a patient with microcephaly, growth restriction, truncal hypotonia, spastic tetraplegia, focal clonic seizures, optic nerve hypoplasia, and brain MRI abnormalities including extremely thin cerebral parenchyma, hypoplastic brain stem, and agenesis of the cerebellum and corpus callosum (Yokoi, 2015). The altered amino acid is conserved throughout evolution: The p.R64 amino acid is conserved in available vertebrate species. The alteration is predicted deleterious by in silico modeling: The p.R64Q alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |