Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000412992 | SCV000492027 | uncertain significance | not specified | 2016-11-18 | criteria provided, single submitter | clinical testing | The c.1678+4A>T variant in the ACADVL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant reduces the quality of the splice donor site in intron 17, and is expected to cause abnormal gene splicing. The c.1678+4A>T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1678+4A>T as a variant of uncertain significance. |
Invitae | RCV001049810 | SCV001213882 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 17 of the ACADVL gene. It does not directly change the encoded amino acid sequence of the ACADVL protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with very long chain acyl-CoA dehydrogenase deficiency (PMID: 30194637). ClinVar contains an entry for this variant (Variation ID: 373435). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Wong Mito Lab, |
RCV001049810 | SCV001365120 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1678+4A>T (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7224556A>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: BP4 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000412992 | SCV002015185 | uncertain significance | not specified | 2021-10-06 | criteria provided, single submitter | clinical testing | Variant summary: ACADVL c.1678+4A>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: two predict the variant abolishes a 5' splicing donor site, while two predict the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 247870 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1678+4A>T has been reported in the literature in individual(s) affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (Miller_2015, Hesse_2018), where one of the reported individuals was noted to carry a potentially pathogenic ACADVL variant on the other allele, and 15% residual enzyme activity measured from patient derived lymphocytes (Hesse_2018). These reports do not provide unequivocal conclusions about association of the variant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ce |
RCV002275020 | SCV002563378 | uncertain significance | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | ACADVL: PM2, PM3, PP4, BP4 |
Natera, |
RCV001049810 | SCV002088810 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2020-07-27 | no assertion criteria provided | clinical testing |