Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002001704 | SCV002276570 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2022-05-09 | 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 174 of the UBA1 protein (p.Arg174Gln). |
Ambry Genetics | RCV002335023 | SCV002642025 | uncertain significance | Inborn genetic diseases | 2021-02-17 | criteria provided, single submitter | clinical testing | The p.R174Q variant (also known as c.521G>A), located in coding exon 5 of the UBA1 gene, results from a G to A substitution at nucleotide position 521. The arginine at codon 174 is replaced by glutamine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.0006% (1/163,879) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.009% (1/11,672) of African/African American alleles. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002479695 | SCV002786445 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy; VEXAS syndrome | 2022-01-24 | criteria provided, single submitter | clinical testing |