ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.1400C>G (p.Pro467Arg) (rs1057521071)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438014 SCV000520933 likely pathogenic not provided 2016-03-03 criteria provided, single submitter clinical testing The P467R variant in the ADSL gene has been reported previously in the presence of a second ADSL missense variant in an individual with Type 1 adenylsuccinate lyase deficiency (Spiegel et al, 2006; Zikanova et al., 2010). The P467R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P467R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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, we interpret P467R as a likely pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000688125 SCV000815725 uncertain significance Adenylosuccinate lyase deficiency 2018-04-17 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 467 of the ADSL protein (p.Pro467Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with ADSL deficiency (PMID: 16839792, 20127976). ClinVar contains an entry for this variant (Variation ID: 381551). Experimental studies in skin fibroblasts from an affected individual have shown that this missense change impairs purinosome assembly (PMID: 22180458). 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.