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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000679862 SCV000961172 pathogenic Adenylosuccinate lyase deficiency 2024-09-01 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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