ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.379C>G (p.Arg127Gly) (rs771794639)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804341 SCV000944245 likely pathogenic Citrullinemia type I 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 127 of the ASS1 protein (p.Arg127Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another ASS1 variant in an individual affected with citrullinemia type I (PMID: 23246278). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the Arg127 amino acid residue in ASS1. Other variant(s) that disrupt this residue have been observed in individuals with ASS1-related conditions (PMID: 23099195, 19006241, 14680976), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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