Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000795220 | SCV000934666 | uncertain significance | Glutaric aciduria, type 1 | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 81 of the GCDH protein (p.Pro81Arg). This variant is present in population databases (rs780408127, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GCDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 641879). 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 GCDH protein function with a positive predictive value of 80%. 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. |
Ambry Genetics | RCV002458424 | SCV002737363 | uncertain significance | Inborn genetic diseases | 2021-10-01 | criteria provided, single submitter | clinical testing | The p.P81R variant (also known as c.242C>G), located in coding exon 3 of the GCDH gene, results from a C to G substitution at nucleotide position 242. The proline at codon 81 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000795220 | SCV001454367 | uncertain significance | Glutaric aciduria, type 1 | 2020-09-16 | no assertion criteria provided | clinical testing |