ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.340T>C (p.Tyr114His) (rs374259530)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186703 SCV000240269 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing The Y114H missense mutation in the ADSL gene has been previously reported in multiple patients with ADSL deficiency who also harbored a second disease-causing mutation in the ADSL gene (Kmoch et al., 2000; Jurecka et al., 2008; Zikanova et al., 2010). This mutation is predicted to alter the catalytic site of the enzyme and result in significantly reduced or absent enzyme activity (Kmoch et al., 2000; Zikanova et al., 2010).
Genetic Services Laboratory, University of Chicago RCV000193076 SCV000246325 pathogenic Adenylosuccinate lyase deficiency 2014-07-16 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415212 SCV000492860 pathogenic Generalized myoclonic seizures; Progressive neurologic deterioration; Inability to walk; Difficulty standing; Severe global developmental delay 2015-06-22 criteria provided, single submitter clinical testing
Invitae RCV000193076 SCV000631367 pathogenic Adenylosuccinate lyase deficiency 2019-11-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 114 of the ADSL protein (p.Tyr114His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs374259530, ExAC 0.007%). This variant has been observed in multiple individuals whom also harbored a second disease-causing mutation in the ADSL gene with findings that are highly specific for adenylosuccinate lyase deficiency (PMID: 10888601, 18524658, 20127976). ClinVar contains an entry for this variant (Variation ID: 204807). Functional studies have shown that this missense change impacts the formation and stability of the purinosome, a multi-enzyme complex that mediates de novo purine synthesis (PMID: 22180458). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000193076 SCV000894267 pathogenic Adenylosuccinate lyase deficiency 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000186703 SCV001249556 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing

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