Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000834 | SCV001157903 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2018-09-21 | criteria provided, single submitter | clinical testing | The ACADVL c.1870G>C; p.Asp624His variant, to our knowledge, is not reported in the medical literature or in gene-specific databases. It is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The aspartic acid at codon 624 is weakly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
| Invitae | RCV001000834 | SCV001517522 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 624 of the ACADVL protein (p.Asp624His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. ClinVar contains an entry for this variant (Variation ID: 811151). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |