Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665265 | SCV000789356 | likely pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2017-02-08 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000009269 | SCV001361811 | likely pathogenic | Mitochondrial trifunctional protein deficiency | 2019-06-14 | criteria provided, single submitter | clinical testing | Variant summary: HADHA c.180+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. Two predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251376 control chromosomes (gnomAD). c.180+1G>A has been reported in the literature in at least one individual affected with Mitochondrial trifunctional protein deficiency with deletion of exon 3 of HADHA cDNA (Brackett_1995, Ibdah_1999). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001382535 | SCV001581366 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-02-13 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 3 of the HADHA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with mitochondrial trifunctional protein deficiency (PMID: 7738175). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 8730). Studies have shown that disruption of this splice site results in skipping of exon 3 and introduces a premature termination codon (PMID: 7738175). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000665265 | SCV004191752 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2023-10-12 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV004566702 | SCV000029487 | pathogenic | Mitochondrial trifunctional protein deficiency 1 | 1995-05-01 | no assertion criteria provided | literature only |