Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001042237 | SCV001205910 | pathogenic | Pyruvate dehydrogenase E3 deficiency | 2023-01-10 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr473Hisfs*6) in the DLD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the DLD protein. This premature translational stop signal has been observed in individual(s) with dihydrolipoamide dehydrogenase deficiency (PMID: 27896107). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DLD protein in which other variant(s) (p.Arg495Gly) have been determined to be pathogenic (PMID: 8968745, 21930696, 27544700). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 840283). |
| Baylor Genetics | RCV001042237 | SCV004193955 | pathogenic | Pyruvate dehydrogenase E3 deficiency | 2023-10-04 | criteria provided, single submitter | clinical testing |