Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001221460 | SCV001393508 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2019-06-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with UBA1-related conditions. This variant is present in population databases (rs781828163, ExAC 0.09%), including at least one homozygous and/or hemizygous individual. This sequence change replaces threonine with alanine at codon 167 of the UBA1 protein (p.Thr167Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. |
| Ambry Genetics | RCV002562526 | SCV003570576 | uncertain significance | Inborn genetic diseases | 2021-08-02 | criteria provided, single submitter | clinical testing | The c.499A>G (p.T167A) alteration is located in exon 6 (coding exon 5) of the UBA1 gene. This alteration results from a A to G substitution at nucleotide position 499, causing the threonine (T) at amino acid position 167 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |