Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521719 | SCV000619346 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001853643 | SCV002174533 | uncertain significance | Adenylosuccinate lyase deficiency | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 286 of the ADSL protein (p.Gln286Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs376912453, ExAC 0.003%). This variant has not been reported in the literature in individuals with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 450734). 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 ADSL protein function. 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. |