ClinVar Miner

Submissions for variant NM_000108.5(DLD):c.1416_1422del (p.Tyr473fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042237 SCV001205910 likely pathogenic Maple syrup urine disease, type 3 2019-04-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the DLD gene (p.Tyr473Hisfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acids of the DLD protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another DLD variant in an individual affected with dihydrolipoamide dehydrogenase deficiency (PMID: 27896107). This variant disrupts the p.Arg495 amino acid residue in DLD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8968745, 21930696, 27544700). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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