Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Wong Mito Lab, |
RCV001200680 | SCV001365001 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.215C>T (NP_000009.1:p.Ser72Phe) [GRCH38: NC_000017.11:g.7220614C>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant dose not meet any evidence codes reported in the ACMG guidelines. |
| Invitae | RCV001200680 | SCV002198634 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-05-22 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 932742). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 24801231). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 72 of the ACADVL protein (p.Ser72Phe). |
| Medical Genetics UMG, |
RCV001200680 | SCV002567994 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-04-03 | criteria provided, single submitter | clinical testing | The c.215C>T (p.Ser72Phe) variant is a missense variant deleterious for prediction algorithms (REVEL score = 0.9409). This variant has a frequency of 0.000003977 in gnomAD database. This variant has been detected by our laboratory in trans with a pathogenic variant in the proband and in other two family members with VLCAD deficiency. This variant has been reported associated with VLCAD deficiency in a published study (PMID: 24801231) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282479 | SCV002571850 | uncertain significance | not specified | 2022-08-08 | criteria provided, single submitter | clinical testing | Variant summary: ACADVL c.215C>T (p.Ser72Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251468 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.215C>T has been reported in the literature in one individual affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. This report does not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV001200680 | SCV002780733 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-04-23 | criteria provided, single submitter | clinical testing |