Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002450354 | SCV002733762 | uncertain significance | Inborn genetic diseases | 2021-05-21 | criteria provided, single submitter | clinical testing | The p.V805I variant (also known as c.2413G>A), located in coding exon 19 of the UBA1 gene, results from a G to A substitution at nucleotide position 2413. The valine at codon 805 is replaced by isoleucine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.0005475% (1/182633) total alleles studied, with 0 hemizygotes observed. The highest observed frequency was 0.001222% (1/81847) of European non-Finnish alleles. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV003101796 | SCV002958036 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2022-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 805 of the UBA1 protein (p.Val805Ile). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with UBA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |