ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.911G>A (p.Arg304Gln)

gnomAD frequency: 0.00005  dbSNP: rs771640767
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002241559 SCV001419826 likely pathogenic Citrullinemia 2024-01-28 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 304 of the ASS1 protein (p.Arg304Gln). This variant is present in population databases (rs771640767, gnomAD 0.009%). This missense change has been observed in individual(s) with citrullinemia type I (Invitae). ClinVar contains an entry for this variant (Variation ID: 970822). 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 not expected to disrupt ASS1 protein function with a negative predictive value of 80%. This variant disrupts the p.Arg304 amino acid residue in ASS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7977368, 12815590, 23246278, 28302489). 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.
Baylor Genetics RCV001246468 SCV004202504 likely pathogenic Citrullinemia type I 2024-03-29 criteria provided, single submitter clinical testing
Natera, Inc. RCV001246468 SCV002085102 uncertain significance Citrullinemia type I 2020-01-23 no assertion criteria provided clinical testing

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