Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186674 | SCV000240240 | likely pathogenic | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect as this variant decreases enzyme stability (Kmoch et al., 2000; Zikanova et al., 2010); This variant is associated with the following publications: (PMID: 10888601, 10090474, 20127976) |
Invitae | RCV000002569 | SCV000960462 | pathogenic | Adenylosuccinate lyase deficiency | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 190 of the ADSL protein (p.Arg190Gln). This variant is present in population databases (rs28941471, gnomAD 0.03%). This missense change has been observed in individual(s) with deficiency of adenylosuccinate lyase (PMID: 10090474, 10888601). ClinVar contains an entry for this variant (Variation ID: 2465). 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 not expected to disrupt ADSL protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ADSL function (PMID: 20127976, 22180458). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000002569 | SCV000022727 | pathogenic | Adenylosuccinate lyase deficiency | 1999-01-01 | no assertion criteria provided | literature only |