Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000442215 | SCV000529547 | uncertain significance | not provided | 2016-07-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ADSL gene. The R196Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R196Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R190Q, R194C) have been reported in the Human Gene Mutation Database in association with ADSL-related disorder (Stenson et al., 2014). However, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Baylor Genetics | RCV001330908 | SCV001522761 | uncertain significance | Adenylosuccinate lyase deficiency | 2023-03-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001330908 | SCV001564809 | uncertain significance | Adenylosuccinate lyase deficiency | 2022-11-02 | 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 196 of the ADSL protein (p.Arg196Gln). This variant is present in population databases (rs753245184, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 387486). 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 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. |
Mayo Clinic Laboratories, |
RCV000442215 | SCV001715630 | uncertain significance | not provided | 2019-10-20 | criteria provided, single submitter | clinical testing |