ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.566A>G (p.Glu189Gly)

gnomAD frequency: 0.00001  dbSNP: rs756363516
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671347 SCV000796312 likely pathogenic Argininosuccinate lyase deficiency 2017-12-11 criteria provided, single submitter clinical testing
Invitae RCV000671347 SCV000943240 pathogenic Argininosuccinate lyase deficiency 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 189 of the ASL protein (p.Glu189Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with argininosuccinate lyase deficiency (PMID: 20236848, 24136197, 31943503). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 555511). 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 with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ASL function (PMID: 21667091, 24136197, 25778938). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000671347 SCV002776162 likely pathogenic Argininosuccinate lyase deficiency 2022-03-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000671347 SCV004202367 pathogenic Argininosuccinate lyase deficiency 2023-10-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV000671347 SCV002076017 likely pathogenic Argininosuccinate lyase deficiency 2020-11-06 no assertion criteria provided clinical testing

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.