ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.953C>T (p.Pro318Leu) (rs202064195)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186684 SCV000240250 likely pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the ADSL gene. The P318L variant has been reported previously in an individual with ADSL deficiency who harbored a second ADSL variant; however phase was undetermined (Marie et al., 2002). The P318L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). 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. The P318L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Illumina Clinical Services Laboratory,Illumina RCV000278336 SCV000438681 uncertain significance Adenylosuccinate lyase deficiency 2018-04-23 criteria provided, single submitter clinical testing The ADSL c.953C>T (p.Pro318Leu) missense variant has been reported in a compound heterozygous state in one individual with adenylosuccinase deficiency (Marie et al. 2002). Functional studies demonstrated reduced (10 - 28%) ADSL activity in cultured skin fibroblasts from the individual. Control data are unavailable for this variant, which is reported at a frequency of 0.00004 in the European (non-Finnish) population of the Exome Aggregation Consortium. The Pro318 residue is conserved across species. Based on the limited evidence, the p.Pro318Leu variant is classified as a variant of unknown significance but suspicious for pathogenicity for adenylosuccinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genetic Services Laboratory, University of Chicago RCV000278336 SCV000593053 likely pathogenic Adenylosuccinate lyase deficiency 2017-04-04 criteria provided, single submitter clinical testing

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