ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.953C>T (p.Pro318Leu)

gnomAD frequency: 0.00001  dbSNP: rs202064195
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186684 SCV000240250 likely pathogenic not provided 2023-06-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16839792, 12016589, 33648541)
Genetic Services Laboratory, University of Chicago RCV000278336 SCV000593053 likely pathogenic Adenylosuccinate lyase deficiency 2017-04-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000278336 SCV002021314 likely pathogenic Adenylosuccinate lyase deficiency 2019-12-12 criteria provided, single submitter clinical testing
Invitae RCV000278336 SCV002296160 pathogenic Adenylosuccinate lyase deficiency 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 318 of the ADSL protein (p.Pro318Leu). This variant is present in population databases (rs202064195, gnomAD 0.004%). This missense change has been observed in individual(s) with adenylosuccinate lyase deficiency (PMID: 12016589, 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: 204792). 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 not expected to disrupt ADSL protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.