Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV001200753 | SCV001365084 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1182+3G>T (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7223240G>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 |
Gene |
RCV001551792 | SCV001772372 | uncertain significance | not provided | 2021-02-03 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 23480858, 27209629) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797826 | SCV002041566 | uncertain significance | not specified | 2021-11-07 | criteria provided, single submitter | clinical testing | Variant summary: ACADVL c.1182+3G>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251454 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1182+3G>T has been reported in the literature in one asymptomatic newborn within a setting of cohort referral because of a suspicion of VLCADD but some uncertainty in diagnosis (example, Schiff_2013 with overlapping reporting by Pena_2016). These report(s) do 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. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001200753 | SCV003522467 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-04-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 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 (rs376281637, gnomAD 0.003%). This variant has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (PMID: 23480858; Invitae). ClinVar contains an entry for this variant (Variation ID: 932804). 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. |
Revvity Omics, |
RCV001200753 | SCV003822468 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2022-05-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001200753 | SCV004212726 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-08-22 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001200753 | SCV002088785 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2021-03-05 | no assertion criteria provided | clinical testing |