Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000818697 | SCV002769784 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2022-12-14 | reviewed by expert panel | curation | The c.1368dup (p.Ile457fs) also known as (p.Ile457HisfsTer6) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one individual with this variant was identified by newborn screen, but this information is insufficient for to use toward classification (PMID: 26385305). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00001549 in the European (non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (VCEP specifications version1; approved November 8, 2021) |
Invitae | RCV000818697 | SCV000959323 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile457Hisfs*6) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 661308). For these reasons, this variant has been classified as Pathogenic. |
Wong Mito Lab, |
RCV000818697 | SCV001364980 | pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2019-11-01 | criteria provided, single submitter | clinical testing | The NM_000018.3:c.1368dupC (NP_000009.1:p.Ile457HisfsTer6) [GRCH38: NC_000017.11:g.7224003dup] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3 |
Baylor Genetics | RCV000818697 | SCV004211798 | likely pathogenic | Very long chain acyl-CoA dehydrogenase deficiency | 2023-04-19 | criteria provided, single submitter | clinical testing |