ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.569G>A (p.Arg190Gln) (rs28941471)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186674 SCV000240240 likely pathogenic not provided 2018-10-05 criteria provided, single submitter clinical testing The R190Q variant in the ADSL gene has been reported in multiple patients with ADSL deficiency who also harbored a second variant in the ADSL gene (Marie et al., 1999; Kmoch et al., 2000). The R190Q variant is observed in 6/17248 (0.035%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). The R190Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Published functional studies demonstrate that the R190Q variant decreases enzyme stability (Kmoch et al., 2000; Zikanova et al., 2010). We interpret R190Q as a likely pathogenic variant.
Invitae RCV000002569 SCV000960462 uncertain significance Adenylosuccinate lyase deficiency 2020-01-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 190 of the ADSL protein (p.Arg190Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs28941471, ExAC 0.06%). This variant has been observed in several individuals affected with deficiency of adenylosuccinate lyase (PMID: 10090474, 10888601). ClinVar contains an entry for this variant (Variation ID: 2465). Experimental studies have provided conflicting results for the effect of this missense variant (p.Arg190Gln) on ADSL function (PMID: 20127976, 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.
OMIM RCV000002569 SCV000022727 pathogenic Adenylosuccinate lyase deficiency 1999-01-01 no assertion criteria provided literature only

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.