Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001315972 | SCV001506569 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 978 of the UBA1 protein (p.Tyr978Cys). This variant is present in population databases (rs782527493, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with UBA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1016899). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002438711 | SCV002750190 | uncertain significance | Inborn genetic diseases | 2022-05-13 | criteria provided, single submitter | clinical testing | The p.Y978C variant (also known as c.2933A>G), located in coding exon 23 of the UBA1 gene, results from an A to G substitution at nucleotide position 2933. The tyrosine at codon 978 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.002% (4/204944) total alleles studied, with no hemizygote(s) observed. The highest observed frequency was 0.005% (1/18838) of African/African American alleles. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |