Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000652042 | SCV000602363 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-02-08 | criteria provided, single submitter | clinical testing | The ACADVL c.1127T>C; p.Phe376Ser variant (rs758928307) is reported in the literature in several individuals affected with diagnosed or suspected VLCAD deficiency, each of whom carried a second missense variant (Merinero 2018, Rovelli 2019). This variant is found in the Latino population with an allele frequency of 0.01% (3/34586 alleles) in the Genome Aggregation Database. The phenylalanine at codon 376 is moderately conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.889). However, due to limited information, the clinical significance of the p.Phe376Ser variant is uncertain at this time. References: Merinero et al. Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers. JIMD Rep. 2018;39:63-74. PMID: 28755359. Rovelli et al. Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2019 May;127(1):64-73. PMID: 31031081. |
Invitae | RCV000652042 | SCV000773906 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 376 of the ACADVL protein (p.Phe376Ser). This variant is present in population databases (rs758928307, gnomAD 0.009%). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 28755359, 31031081). 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: 203581). 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%. For these reasons, this variant has been classified as Pathogenic. |
Wong Mito Lab, |
RCV000652042 | SCV001365079 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1127T>C (NP_000009.1:p.Phe376Ser) [GRCH38: NC_000017.11:g.7223182T>C] 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 |
Mendelics | RCV000652042 | SCV002517504 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000652042 | SCV004216891 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-06-20 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000652042 | SCV002088780 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2020-11-13 | no assertion criteria provided | clinical testing |