ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.338G>A (p.Arg113Gln)

gnomAD frequency: 0.00002  dbSNP: rs752783461
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670964 SCV000795892 likely pathogenic Argininosuccinate lyase deficiency 2017-11-29 criteria provided, single submitter clinical testing
Invitae RCV000670964 SCV002245780 pathogenic Argininosuccinate lyase deficiency 2023-09-29 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 113 of the ASL protein (p.Arg113Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with argininosuccinic aciduria (PMID: 17326097). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 555191). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ASL protein function. Experimental studies have shown that this missense change affects ASL function (PMID: 31943503). This variant disrupts the p.Arg113 amino acid residue in ASL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10896281, 24166829). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000670964 SCV004202400 pathogenic Argininosuccinate lyase deficiency 2023-10-22 criteria provided, single submitter clinical testing

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