Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001905335 | SCV002133949 | uncertain significance | not provided | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 218 of the USB1 protein (p.Ala218Val). This variant is not present in population databases (gnomAD no frequency). 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: 1364316). 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 | RCV004968382 | SCV005530784 | uncertain significance | Inborn genetic diseases | 2024-11-25 | criteria provided, single submitter | clinical testing | The p.A218V variant (also known as c.653C>T), located in coding exon 6 of the USB1 gene, results from a C to T substitution at nucleotide position 653. The alanine at codon 218 is replaced by valine, an amino acid with similar 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. |