Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001300608 | SCV001489754 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2023-06-16 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1003979). This variant has not been reported in the literature in individuals affected with UBA1-related conditions. This variant is present in population databases (rs781803482, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 245 of the UBA1 protein (p.Gly245Arg). |
Ambry Genetics | RCV002384356 | SCV002670369 | uncertain significance | Inborn genetic diseases | 2020-08-12 | criteria provided, single submitter | clinical testing | The p.G245R variant (also known as c.733G>A), located in coding exon 7 of the UBA1 gene, results from a G to A substitution at nucleotide position 733. The glycine at codon 245 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. Based on data from gnomAD, the c.733G>A variant has an overall frequency of 0.002% (4/205,086) of total alleles studied with the highest observed frequency of 0.01% (2/19,027) in the African sub-population. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |