ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.253C>T (p.Arg85Ter)

gnomAD frequency: 0.00001  dbSNP: rs1036185928
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434653 SCV000515726 pathogenic not provided 2022-07-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10888601, 25326635, 20177786, 30185235)
Baylor Genetics RCV000679862 SCV000807227 pathogenic Adenylosuccinate lyase deficiency 2017-09-01 criteria provided, single submitter clinical testing This nonsense mutation was identified in trans with a splice mutation in a 2-year-old male with failure to thrive, short stature, problems with vomiting and hypoglycemia, postprandial hyperglycemia, and normal developmental milestones.
Invitae RCV000679862 SCV000961172 pathogenic Adenylosuccinate lyase deficiency 2023-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg85*) in the ADSL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADSL are known to be pathogenic (PMID: 10888601, 20177786). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with West syndrome (PMID: 30185235). ClinVar contains an entry for this variant (Variation ID: 379129). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago RCV000434653 SCV003839337 pathogenic not provided 2022-12-13 no assertion criteria provided clinical testing DNA sequence analysis of the ADSL gene demonstrated a sequence change, c.253C>T, which results in the creation of a premature stop codon at amino acid position 85, p.Arg85*. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ADSL protein with potentially abnormal function. This sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.0004% (dbSNP rs1036185928). This sequence change has previously been described in the compound heterozygous state with a second variant in ADSL in an individual with West syndrome (PMID: 30185235) and in association with childhood epilepsy (PMID: 31440721). Loss of function variants in ADSL have been reported to be pathogenic (PMID: 10888601, 28487569, 20177786). These collective evidences indicate that this sequence change is pathogenic.

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