Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001046258 | SCV001210154 | uncertain significance | not provided | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 252 of the USB1 protein (p.Arg252Ser). This variant is present in population databases (rs146419360, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with USB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 843594). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt USB1 protein function with a negative predictive value of 80%. 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 | RCV004963023 | SCV005530821 | uncertain significance | Inborn genetic diseases | 2025-01-08 | criteria provided, single submitter | clinical testing | The p.R252S variant (also known as c.754C>A), located in coding exon 7 of the USB1 gene, results from a C to A substitution at nucleotide position 754. The arginine at codon 252 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |