Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672204 | SCV000797285 | uncertain significance | Glutaric aciduria, type 1 | 2018-02-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000672204 | SCV001774725 | pathogenic | Glutaric aciduria, type 1 | 2021-07-19 | criteria provided, single submitter | clinical testing | Variant summary: GCDH c.536T>G (p.Leu179Arg) results in a non-conservative amino acid change located in the Acyl-CoA oxidase/dehydrogenase, central domain (IPR006091) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251298 control chromosomes (gnomAD). c.536T>G has been reported in the literature in multiple individuals (including homozygous occurrences) affected with Glutaric Acidemia Type 1 (Goodman_1998; Tamhankar_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV000672204 | SCV003443177 | pathogenic | Glutaric aciduria, type 1 | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 179 of the GCDH protein (p.Leu179Arg). This variant is present in population databases (rs774526353, gnomAD 0.01%). This missense change has been observed in individual(s) with glutaric aciduria type 1 (PMID: 34504725). ClinVar contains an entry for this variant (Variation ID: 556229). 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. For these reasons, this variant has been classified as Pathogenic. |
| Center for Genomic Medicine, |
RCV000672204 | SCV004807052 | uncertain significance | Glutaric aciduria, type 1 | 2024-03-26 | criteria provided, single submitter | clinical testing |