ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.1135C>T (p.Arg379Cys) (rs28940287)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185769 SCV000238700 pathogenic not provided 2021-08-05 criteria provided, single submitter clinical testing Published functional studies demonstrate that R379C is predicted to affect the stability of the argininosuccinate lyase enzyme and is associated with 10% of wild-type argininosuccinate lyase activity (Hu et al., 2015; Engel et al., 2012); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31943503, 31589614, 32152836, 20236848, 12408190, 27515243, 28643139, 26745957, 24166829, 12384776, 25778938, 21667091, 25087612)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000185769 SCV000700800 likely pathogenic not provided 2016-12-22 criteria provided, single submitter clinical testing
Invitae RCV000002504 SCV000756207 pathogenic Argininosuccinate lyase deficiency 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 379 of the ASL protein (p.Arg379Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs28940287, ExAC 0.01%). This variant has been observed as homozygous or in combination with another ASL variant in individuals affected with argininosuccinic aciduria, including co-occurrence on the opposite chromosome (in trans) from a pathogenic ASL variant in one case (PMID: 12408190, 20236848, 27515243, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 2403). Experimental studies have shown that this missense change leads to a reduction in ASL enzymatic activity in vitro (PMID: 25778938, 21667091). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000002504 SCV001520222 likely pathogenic Argininosuccinate lyase deficiency 2020-03-26 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
OMIM RCV000002504 SCV000022662 pathogenic Argininosuccinate lyase deficiency 2002-09-01 no assertion criteria provided literature only
Natera, Inc. RCV000002504 SCV001459678 pathogenic Argininosuccinate lyase deficiency 2020-09-16 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.