ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.332G>A (p.Arg111Gln) (rs561367199)

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
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000493464 SCV000342981 uncertain significance not provided 2016-06-30 criteria provided, single submitter clinical testing
GeneDx RCV000493464 SCV000582822 likely pathogenic not provided 2016-04-15 criteria provided, single submitter clinical testing The R111Q variant has been published in a patient with argininosuccinic aciduria who was homozygous for R111Q and who was diagnosed following an abnormal newborn screening result (Al-Shamsi et al. 2014). The R111Q variant was not observed with any significant frequency in either the 1000 Genomes Project Consortium or in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R111Q 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl RCV000668710 SCV000793354 uncertain significance Argininosuccinate lyase deficiency 2017-08-23 criteria provided, single submitter clinical testing
Invitae RCV000668710 SCV001490401 uncertain significance Argininosuccinate lyase deficiency 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 111 of the ASL protein (p.Arg111Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs561367199, ExAC 0.05%). This variant has been observed in individual(s) with argininosuccinate lyase deficiency (PMID: 24516753). ClinVar contains an entry for this variant (Variation ID: 288770). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg111 amino acid residue in ASL. Other variant(s) that disrupt this residue have been observed in individuals with ASL-related conditions (PMID: 1705937), which suggests that this may be a clinically significant amino acid residue. 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.

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.