Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001330907 | SCV001522760 | uncertain significance | Adenylosuccinate lyase deficiency | 2020-09-02 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Mayo Clinic Laboratories, |
RCV001509099 | SCV001715629 | uncertain significance | not provided | 2019-10-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001330907 | SCV003322781 | pathogenic | Adenylosuccinate lyase deficiency | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 168 of the ADSL protein (p.Val168Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with adenylosuccinate lyase deficiency (PMID: 33648541). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1029580). 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. For these reasons, this variant has been classified as Pathogenic. |