Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000623886 | SCV000740752 | pathogenic | Inborn genetic diseases | 2014-10-14 | criteria provided, single submitter | clinical testing | The c.283G>T (p.G95C) alteration is located in exon 3 (coding exon 3) of the TUBA1A gene. This alteration results from a G to T substitution at nucleotide position 283, causing the glycine (G) at amino acid position 95 to be replaced by a cysteine (C). The alteration is not observed in healthy cohorts: Based on data from the NHLBI Exome Sequencing Project (ESP), the TUBA1A c.283G>T alteration was not observed among 6,477 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP). Though some variants may appear to be rare due to database-specific ethnic underrepresentation, rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012). IF USED, PULL THESE INTO REFERENCES: Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. The altered nucleotide is conserved throughout evolution: The c.283G nucleotide is completely conserved in available vertebrate species. The altered amino acid is conserved throughout evolution: The p.G95 amino acid is completely conserved in available vertebrate species. The c.283G>T (p.G95C) alteration is located in coding exon 3 of the TUBA1A gene. The alteration consists of a G to T substitution at nucleotide position 283, causing the Glycine (G) at amino acid position 95 to be replaced by a Cysteine (C). The alteration is predicted deleterious by in silico models: The p.G95C alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses. The alteration is predicted not to affect splicing by in silico models: Based on BDGP and ESEfinder splice site in silico tools, this alteration does not have any significant effect on the native acceptor/donor splice site; however, direct evidence is unavailable Based on the available evidence, this alteration is classified as pathogenic. |
| Institute of Human Genetics, |
RCV000767498 | SCV000898113 | 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 born individual of unknown sex. The c.283G>T, p.(Gly95Cys) variant has been reported as a variant of de novo origin. This variant and associated phenotype was previously reported by Helbig et al. Genet Med, 2016 HPO-standardized clinical features were: Generalized tonic-clonic seizures (HP:0002069) |