Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589800 | SCV000695943 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2017-06-26 | criteria provided, single submitter | clinical testing | Variant summary: The HADHA c.871C>T (p.Arg291X) variant results in a premature termination codon, predicted to cause a truncated or absent HADHA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 121364 control chromosomes. Multiple publications have cited the variant in affected individuals, along with functional studies indicating no detectable protein levels were observed (Ibdah_1998). In addition, a reputable database classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Labcorp Genetics |
RCV000819036 | SCV000959677 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg291*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with trifunctional protein deficiency (PMID: 9739053). ClinVar contains an entry for this variant (Variation ID: 8737). 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. |
Baylor Genetics | RCV000589800 | SCV004191797 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-03-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004018604 | SCV004880305 | pathogenic | Inborn genetic diseases | 2023-12-14 | criteria provided, single submitter | clinical testing | The c.871C>T (p.R291*) alteration, located in exon 9 (coding exon 9) of the HADHA gene, consists of a C to T substitution at nucleotide position 871. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 291. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been detected in conjunction with a HADHA variant in two individuals a diagnosis of LCHAD deficiency and in one individual with clinical features of MTP; however, the phase of the two variants was not specified (Ibdah, 1998; Waisbren, 2013; Squires, 2023). Based on the available evidence, this alteration is classified as pathogenic. |
OMIM | RCV004566707 | SCV000029494 | pathogenic | Mitochondrial trifunctional protein deficiency 1 | 1998-09-15 | no assertion criteria provided | literature only | |
Counsyl | RCV000589800 | SCV001132410 | likely pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2015-04-08 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000589800 | SCV002076519 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2020-12-27 | no assertion criteria provided | clinical testing |