ClinVar Miner

Submissions for variant NM_000018.3(ACADVL):c.1375dup (rs796051916)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185739 SCV000238667 pathogenic not provided 2017-09-18 criteria provided, single submitter clinical testing The c.1375dupC pathogenic variant in the ACADVL gene has been reported previously in individuals with a positive newborn screen for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Miller et al., 2015). The c.1375dupC variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The duplication causes a frameshift starting with codon Arginine 459, changes this amino acid to a Proline residue and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Arg459ProfsX4. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.1375dupC as pathogenic.
Invitae RCV000538432 SCV000654931 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-05-24 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 14 of the ACADVL mRNA (c.1375dupC), causing a frameshift at codon 459. This creates a premature translational stop signal (p.Arg459Profs*4) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic. This particular variant has been reported in the literature  in individuals with suspected very long chain acyl-coA dehydrogenase deficiency after positive new born screening (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 203592). This variant is also known as c.1375_1376insC in the literature. For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185739 SCV000700259 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing

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