Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001338582 | SCV001532262 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2020-02-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with UBA1-related conditions. 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 (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. This variant is present in population databases (rs782051479, ExAC 0.002%). This sequence change replaces alanine with glutamic acid at codon 372 of the UBA1 protein (p.Ala372Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. |