Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493353 | SCV000582011 | likely pathogenic | not provided | 2015-07-22 | criteria provided, single submitter | clinical testing | The G703R variant has published previously in a patient who had an abnormal newborn screening result for long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency who also harbored the E510Q variant (Sykut-Cegielska et al. 2011). The G703R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (D701G) has been reported in the Human Gene Mutation Database in association with mitochondrial trifunctional protein (MTP) deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, the G703R variant was interpreted to be a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Ce |
RCV000493353 | SCV000608925 | uncertain significance | not provided | 2017-03-01 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000667879 | SCV000792391 | uncertain significance | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2017-06-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001865540 | SCV002263379 | pathogenic | Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 703 of the HADHA protein (p.Gly703Arg). This variant is present in population databases (rs200438844, gnomAD 0.01%). This missense change has been observed in individual(s) with HADHA-related conditions and/or mitochondrial trifunctional protein deficiency (PMID: 21103935, 26109258, 34878152). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 429439). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HADHA protein function. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000667879 | SCV004191746 | pathogenic | Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency | 2024-02-25 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV004568621 | SCV003840967 | pathogenic | Mitochondrial trifunctional protein deficiency 1 | 2023-03-27 | no assertion criteria provided | literature only |