Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002638028 | SCV003516980 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2022-10-20 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with UBA1-related conditions. This variant is present in population databases (rs782727078, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 758 of the UBA1 protein (p.Asn758Ser). |
| Ambry Genetics | RCV004070805 | SCV004975321 | likely benign | Inborn genetic diseases | 2023-12-08 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |