Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820848 | SCV000961580 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-02-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg560*) 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 (rs137852771, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with mitochondrial trifunctional protein deficiency (PMID: 8865274, 27491397). ClinVar contains an entry for this variant (Variation ID: 8732). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000009271 | SCV001361810 | pathogenic | Mitochondrial trifunctional protein deficiency | 2019-01-14 | criteria provided, single submitter | clinical testing | Variant summary: HADHA c.1678C>T (p.Arg560X) 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 2e-05 in 246244 control chromosomes (gnomAD). c.1678C>T has been reported in the literature in homozygote and compound heterozygote individuals affected with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (Boutron_2011, Boese_2016). The homozygote patient was found at a have a tritiated-palmitate levels of 13% and 3H-Pal/3H-Myr: normalized ratio between [9,10-3H]-palmitate and [9,10-3H]-myristate detritiation (both results expressed as percentages of the controls mean) of 0.6. This ratio is >0.85 in controls and other long chain fatty acid oxidation defects. 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 pathogenic. |
| Laboratory of Medical Genetics, |
RCV001729343 | SCV001976685 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2021-10-01 | criteria provided, single submitter | clinical testing | PVS1, PM2, PP5 |
| Fulgent Genetics, |
RCV005003346 | SCV002794472 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Mitochondrial trifunctional protein deficiency 1 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001729343 | SCV004191758 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-03-14 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV004566704 | SCV000029489 | pathogenic | Mitochondrial trifunctional protein deficiency 1 | 1996-09-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV001729343 | SCV002076506 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2020-07-29 | no assertion criteria provided | clinical testing |