Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489046 | SCV000577722 | likely pathogenic | not provided | 2015-06-16 | criteria provided, single submitter | clinical testing | The G280E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G280E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function, and a missense variant in a nearby residue (Q286R) has been reported in the Human Gene Mutation Database in association with argininosuccinic aciduria (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, the G280E variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Counsyl | RCV000669138 | SCV000793854 | uncertain significance | Argininosuccinate lyase deficiency | 2017-09-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000669138 | SCV002197884 | uncertain significance | Argininosuccinate lyase deficiency | 2020-11-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ASL-related conditions. ClinVar contains an entry for this variant (Variation ID: 427091). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 280 of the ASL protein (p.Gly280Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |