The relationship between ASL and argininosuccinic aciduria (autosomal recessive inheritance) was evaluated using the ClinGen Clinical Validity Framework as of August 28, 2018. Variants in ASL were first reported in humans with this disease as early as 1990 (Walker et al., PMID 2263616) At least 100 unique variants (e.g. missense, in-frame indel, nonsense, frameshift, splice site, etc) have been reported in humans. Supporting evidence includes case-level data (12 points) and experimental data (6 points). Variants in this gene were curated from 3 publications (Walker et al. 1990, PMID 2263616; Trevisson et al. 2007, PMID 17326097; Trevisson et al, 2009; PMID 19703900). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. The mechanism for disease is biallelic loss of function. This gene-disease relationship is supported by the biochemical function of the gene product, argininosuccinate lyase (PMIDs 4732887, 21312326, 22081021, 31110235), and by the clinical and biochemical features observed in a null and hypomorphic mouse models (PMIDs 12559843, 22081021). In summary, ASL is definitively associated with argininosuccinate lyase deficiency. This classification was approved by the ClinGen Aminoacidopathy Expert Panel on September 5th, 2018.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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