Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667698 | SCV000792190 | likely pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2017-06-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000667698 | SCV000917467 | likely pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2018-01-29 | criteria provided, single submitter | clinical testing | Variant summary: HADHA c.72delT (p.Tyr24X) 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 classified as pathogenic by our laboratory (eg. p.R291X and p.L656X). The variant allele was found at a frequency of 4.1e-06 in 246080 control chromosomes in gnomAD, which does not exceed the maximal expected allele frequency for a pathogenic variant in HADHA. The variant c.72delT has been reported in the literature in individuals affected with Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (SPIEKERKOETTER_2004). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined here, the variant was classified as likely pathogenic. |
Invitae | RCV001855485 | SCV002245799 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2021-10-04 | 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: 552438). This premature translational stop signal has been observed in individual(s) with mitochondrial trifunctional protein deficiency (PMID: 14630990). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr24*) 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). |
Ce |
RCV003222091 | SCV003918207 | pathogenic | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | HADHA: PVS1, PM2, PM3:Supporting, PS4:Supporting |