Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000444441 | SCV000513123 | pathogenic | not provided | 2017-01-11 | criteria provided, single submitter | clinical testing | The R132Q variant in the GCDH gene has previously been reported in association with GA1 in several unrelated individuals (Zschocke et al., 2000; Busquets et al., 2000; Wang et al., 2013). The R132Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret R132Q to be a pathogenic variant. |
Invitae | RCV000553882 | SCV000631935 | pathogenic | Glutaric aciduria, type 1 | 2024-01-04 | 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 132 of the GCDH protein (p.Arg132Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glutaryl-CoA dehydrogenase deficiency (PMID: 10699052, 10960496, 24332224, 34344405; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 377917). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GCDH protein function. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000553882 | SCV000894184 | likely pathogenic | Glutaric aciduria, type 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000553882 | SCV004199206 | pathogenic | Glutaric aciduria, type 1 | 2023-09-13 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000553882 | SCV001132396 | likely pathogenic | Glutaric aciduria, type 1 | 2019-01-09 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000553882 | SCV001454370 | pathogenic | Glutaric aciduria, type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |