ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.1678C>T (p.Arg560Ter)

gnomAD frequency: 0.00002  dbSNP: rs137852771
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820848 SCV000961580 pathogenic Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2023-07-26 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: 8732). This premature translational stop signal has been observed in individuals with mitochondrial trifunctional protein deficiency (PMID: 8865274, 27491397). This variant is present in population databases (rs137852771, gnomAD 0.003%). 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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, National & Kapodistrian University of Athens RCV001729343 SCV001976685 pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2021-10-01 criteria provided, single submitter clinical testing PVS1, PM2, PP5
Fulgent Genetics, Fulgent Genetics RCV000820848 SCV002794472 pathogenic Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2022-01-26 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, Inc. RCV001729343 SCV002076506 pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2020-07-29 no assertion criteria provided clinical testing

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