Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001206495 | SCV001377805 | pathogenic | Lipoic acid synthetase deficiency | 2022-10-05 | 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: 937476). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr148Aspfs*12) in the LIAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIAS are known to be pathogenic (PMID: 24334290, 27923773). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001206495 | SCV004122819 | pathogenic | Lipoic acid synthetase deficiency | 2023-10-12 | criteria provided, single submitter | clinical testing | Variant summary: LIAS c.440dupA (p.Thr148AspfsX12) 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 was absent in 251324 control chromosomes. To our knowledge, no occurrence of c.440dupA in individuals affected with Pyruvate Dehydrogenase Lipoic Acid Synthetase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |