ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.380G>T (p.Arg127Leu)

dbSNP: rs201623252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV000665366 SCV001426526 pathogenic Citrullinemia type I criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003594016 SCV004295580 likely pathogenic Citrullinemia 2023-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 127 of the ASS1 protein (p.Arg127Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Citrullinemia (PMID: 24889030, 32860008). ClinVar contains an entry for this variant (Variation ID: 550586). 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 ASS1 protein function. Experimental studies have shown that this missense change affects ASS1 function (PMID: 27287393). This variant disrupts the p.Arg127 amino acid residue in ASS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14680976, 23099195, 28111830, 31208364). 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.
Counsyl RCV000665366 SCV000789477 uncertain significance Citrullinemia type I 2017-02-07 no assertion criteria provided clinical testing This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000665366 SCV001132908 pathogenic Citrullinemia type I 2019-08-25 no assertion criteria provided clinical testing

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