Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004971906 | SCV005530807 | uncertain significance | Inborn genetic diseases | 2024-12-06 | criteria provided, single submitter | clinical testing | The p.R144C variant (also known as c.430C>T), located in coding exon 3 of the USB1 gene, results from a C to T substitution at nucleotide position 430. The arginine at codon 144 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV005109992 | SCV005812205 | uncertain significance | not provided | 2024-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 144 of the USB1 protein (p.Arg144Cys). This variant is present in population databases (rs774644058, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with USB1-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |