Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001054138 | SCV001218437 | pathogenic | 3-methylglutaconic aciduria type 1 | 2023-04-24 | 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: 850052). This variant has not been reported in the literature in individuals affected with AUH-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gly66Alafs*6) in the AUH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AUH are known to be pathogenic (PMID: 12655555, 20882351). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001054138 | SCV004020850 | pathogenic | 3-methylglutaconic aciduria type 1 | 2023-06-14 | criteria provided, single submitter | clinical testing | Variant summary: AUH c.197delG (p.Gly66AlafsX6) 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. The variant allele was found at a frequency of 2.9e-05 in 169544 control chromosomes. To our knowledge, no occurrence of c.197delG in individuals affected with AUH-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |