Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000419557 | SCV000224785 | uncertain significance | not provided | 2015-01-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000419557 | SCV000521169 | likely pathogenic | not provided | 2018-11-02 | criteria provided, single submitter | clinical testing | The Q333E missense change in the GCDH gene has been previously reported as disease-causing (Goodman et al., 1998). Q333E is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. It occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The Q333E variant is predicted to be located on the surface of the GCDH gene and to be involved in GCDH homotetramerisation; approximately 20% of missense variants reported in association with GA1 are located on the surface of GCDH, supporting the functional importance of this region of the protein (Schmiesing et al., 2017). In summary, we interpret Q333E as likely pathogenic. |
| Counsyl | RCV000675103 | SCV000800645 | uncertain significance | Glutaric aciduria, type 1 | 2018-01-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000675103 | SCV000955272 | uncertain significance | Glutaric aciduria, type 1 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 333 of the GCDH protein (p.Gln333Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with glutaric aciduria (PMID: 9711871). ClinVar contains an entry for this variant (Variation ID: 193561). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |