Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000668964 | SCV001207156 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 416 of the ACADVL protein (p.Ala416Ser). This variant is present in population databases (rs118204018, gnomAD 0.002%). This missense change has been observed in individual(s) with VLCAD deficiency (PMID: 25456746). This variant is also known as p.A376S. ClinVar contains an entry for this variant (Variation ID: 553497). 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 ACADVL protein function with a positive predictive value of 95%. This variant disrupts the p.Ala416 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11158518, 11914034, 15210884). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Wong Mito Lab, |
RCV000668964 | SCV001365092 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1246G>T (NP_000009.1:p.Ala416Ser) [GRCH38: NC_000017.11:g.7223707G>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PP3 |
Myriad Genetics, |
RCV000668964 | SCV002060394 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2021-10-20 | criteria provided, single submitter | clinical testing | NM_000018.3(ACADVL):c.1246G>T(A416S) is a missense variant classified as a variant of uncertain significance in the context of very-long-chain acyl-CoA dehydrogenase deficiency. A416S has been observed in cases with relevant disease (PMID: 25456746, 26385305, 30194637). Functional assessments of this variant are not available in the literature. A416S has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, there is insufficient evidence to classify NM_000018.3(ACADVL):c.1246G>T(A416S) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Baylor Genetics | RCV000668964 | SCV004214018 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-10-30 | criteria provided, single submitter | clinical testing |