Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169495 | SCV000220952 | likely pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2014-12-11 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193146 | SCV001361812 | likely pathogenic | Mitochondrial trifunctional protein deficiency | 2019-10-31 | criteria provided, single submitter | clinical testing | Variant summary: HADHA c.1981_1999del19 (p.Leu661SerfsX12) 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 reported in patients (HGMD). This exonic variant is located close to a canonical splice-site and therefore could affect mRNA splicing: 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251460 control chromosomes. c.1981_1999del19 has been reported in the literature in a compound heterozygous individual affected with Mitochondrial trifunctional protein deficiency (Boutron_2011). This publication reported that the patient carried this variant had 39% of normal LCHAD activity measured from muscle tissue (Boutron_2011). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002498845 | SCV002811661 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2022-01-19 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000169495 | SCV004191777 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2023-06-08 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002498845 | SCV004569108 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu661Serfs*12) in the HADHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HADHA are known to be pathogenic (PMID: 7738175, 21103935, 21549624, 22459206). This variant is present in population databases (rs749848370, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with HADHA-related conditions (PMID: 21549624, 32827528). ClinVar contains an entry for this variant (Variation ID: 189089). For these reasons, this variant has been classified as Pathogenic. |