Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV002248971 | SCV002516229 | likely pathogenic | Argininosuccinate lyase deficiency | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002248971 | SCV003000760 | likely pathogenic | Argininosuccinate lyase deficiency | 2023-09-08 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ile100 amino acid residue in ASL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12384776, 18616627, 22231378). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt ASL protein function. ClinVar contains an entry for this variant (Variation ID: 1685244). This variant has not been reported in the literature in individuals affected with ASL-related conditions. This variant is present in population databases (rs202142867, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 100 of the ASL protein (p.Ile100Asn). |