ClinVar Miner

Submissions for variant NM_000048.4(ASL):c.577C>T (p.Arg193Trp)

gnomAD frequency: 0.00003  dbSNP: rs1428029508
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668596 SCV000793225 uncertain significance Argininosuccinate lyase deficiency 2017-08-07 criteria provided, single submitter clinical testing
Invitae RCV000668596 SCV001585629 pathogenic Argininosuccinate lyase deficiency 2023-07-25 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.007%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg193 amino acid residue in ASL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1705937, 12408190, 24166829, 25778938). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects ASL function (PMID: 25778938). 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. ClinVar contains an entry for this variant (Variation ID: 553200). This missense change has been observed in individuals with argininosuccinate lyase deficiency (PMID: 24166829). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 193 of the ASL protein (p.Arg193Trp).
Baylor Genetics RCV000668596 SCV004201195 likely pathogenic Argininosuccinate lyase deficiency 2023-04-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV000668596 SCV002076021 pathogenic Argininosuccinate lyase deficiency 2020-05-13 no assertion criteria provided clinical testing

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