Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001325437 | SCV001516429 | uncertain significance | Infantile-onset X-linked spinal muscular atrophy | 2023-09-03 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1025156). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 288 of the UBA1 protein (p.Arg288His). 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 variant has not been reported in the literature in individuals affected with UBA1-related conditions. 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 tolerated. 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. |
Ambry Genetics | RCV002377417 | SCV002687794 | uncertain significance | Inborn genetic diseases | 2022-05-22 | criteria provided, single submitter | clinical testing | The p.R288H variant (also known as c.863G>A), located in coding exon 8 of the UBA1 gene, results from a G to A substitution at nucleotide position 863. The arginine at codon 288 is replaced by histidine, an amino acid with highly similar properties. Based on data from gnomAD, the X allele has an overall frequency of 0.002221% (4/180139) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was 0.007282% (1/13733) of East Asian alleles. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |