Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000539996 | SCV000631871 | likely pathogenic | Argininosuccinate lyase deficiency | 2023-06-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 225 of the ASL protein (p.Ile225Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with highly specific biochemical findings suggestive of argininosuccinic aciduria (Invitae). ClinVar contains an entry for this variant (Variation ID: 459921). 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. 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. |
Natera, |
RCV000539996 | SCV002076026 | uncertain significance | Argininosuccinate lyase deficiency | 2021-05-26 | no assertion criteria provided | clinical testing |