Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410967 | SCV000485332 | likely pathogenic | Glutaric aciduria, type 1 | 2015-11-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000760423 | SCV000890301 | pathogenic | not provided | 2018-07-27 | criteria provided, single submitter | clinical testing | The Q76X variant has been published in association with gluratric aciduria type 1 (Mushimoto et al. 2011). The variant is not observed in large population cohorts (Lek et al., 2016). The Q76X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant as pathogenic. |
| Invitae | RCV000410967 | SCV001391093 | pathogenic | Glutaric aciduria, type 1 | 2023-06-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370102). This premature translational stop signal has been observed in individual(s) with GCDH-related conditions (PMID: 10699052, 21176883). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln76*) in the GCDH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCDH are known to be pathogenic (PMID: 10699052, 11854167, 16602100). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410967 | SCV002600562 | pathogenic | Glutaric aciduria, type 1 | 2022-10-03 | criteria provided, single submitter | clinical testing | Variant summary: GCDH c.226C>T (p.Gln76X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251416 control chromosomes. c.226C>T has been reported in the literature in individuals affected with Glutaric Acidemia Type 1. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000410967 | SCV004199279 | pathogenic | Glutaric aciduria, type 1 | 2022-06-15 | criteria provided, single submitter | clinical testing |