Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001312513 | SCV001502969 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2020-07-09 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 247 of the UBA1 protein (p.Phe247Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002384387 | SCV002671637 | uncertain significance | Inborn genetic diseases | 2021-05-17 | criteria provided, single submitter | clinical testing | The p.F247L variant (also known as c.741T>G), located in coding exon 7 of the UBA1 gene, results from a T to G substitution at nucleotide position 741. The phenylalanine at codon 247 is replaced by leucine, an amino acid with highly similar properties. Based on data from gnomAD, the X allele has an overall frequency of 0.004541% (1/22022) total alleles studied, with 0 hemizygotes observed. The highest observed frequency was 0.009216% (1/10851) of European (non-Finnish) alleles. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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. |