Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001934531 | SCV002135014 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2021-10-12 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs781997101, ExAC 0.002%). This sequence change replaces arginine with cysteine at codon 957 of the UBA1 protein (p.Arg957Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant has not been reported in the literature in individuals affected 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 disruptive. |