Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669909 | SCV000794709 | uncertain significance | Argininosuccinate lyase deficiency | 2017-10-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000669909 | SCV004280482 | likely pathogenic | Argininosuccinate lyase deficiency | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 297 of the ASL protein (p.Arg297Gln). This variant is present in population databases (rs750431938, gnomAD 0.002%). This missense change has been observed in individual(s) with argininosuccinate lyase deficiency (PMID: 19703900). ClinVar contains an entry for this variant (Variation ID: 554299). 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. Experimental studies have shown that this missense change affects ASL function (PMID: 19703900). This variant disrupts the p.Arg297 amino acid residue in ASL. Other variant(s) that disrupt this residue have been observed in individuals with ASL-related conditions (PMID: 12384776), which suggests that this may be a clinically significant amino acid residue. 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. |