ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.1367G>A (p.Arg456Gln)

gnomAD frequency: 0.00003  dbSNP: rs767271619
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000666207 SCV002303227 likely pathogenic Argininosuccinate lyase deficiency 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 456 of the ASL protein (p.Arg456Gln). This variant is present in population databases (rs767271619, gnomAD 0.03%). This missense change has been observed in individual(s) with argininosuccinate lyase deficiency (PMID: 24166829, 31943503). ClinVar contains an entry for this variant (Variation ID: 551210). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ASL protein function with a positive predictive value of 95%. This variant disrupts the p.Arg456 amino acid residue in ASL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17326097). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000666207 SCV004028495 likely pathogenic Argininosuccinate lyase deficiency 2023-02-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666207 SCV004208740 pathogenic Argininosuccinate lyase deficiency 2024-03-20 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000666207 SCV004238474 likely pathogenic Argininosuccinate lyase deficiency 2023-07-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000666207 SCV005667434 likely pathogenic Argininosuccinate lyase deficiency 2024-01-30 criteria provided, single submitter clinical testing
Counsyl RCV000666207 SCV000790460 uncertain significance Argininosuccinate lyase deficiency 2017-03-21 flagged submission clinical testing

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