ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.887_888del (p.Pro296fs) (rs753108198)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169392 SCV000220784 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2014-10-10 criteria provided, single submitter literature only
GeneDx RCV000185736 SCV000238664 pathogenic not provided 2014-07-25 criteria provided, single submitter clinical testing The c.887_888delCT mutation has been reported previously in association with VLCAD deficiency (Mathur et al., 1999). The deletion causes a frameshift starting with codon Proline 296, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Pro296ArgfsX17. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in ACADVL panel(s).
Integrated Genetics/Laboratory Corporation of America RCV000169392 SCV000693968 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-05-29 criteria provided, single submitter clinical testing Variant summary: The ACADVL c.887_888delCT (p.Pro296Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent ACADVL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been submitted and classified as pathogenic by laboratories in ClinVar (e.g. c.1113delG (p.Ile373Phefs), c.1592dupG (p.Ser532Glufs), c.1807dupT (p.Cys603Leufs), c.1806_1807delCT (p.Cys603Terfs), etc.). This variant was found in 3/108520 control chromosomes from ExAC at a frequency of 0.0000276, which does not exceed the estimated maximal expected allele frequency of a pathogenic ACADVL variant (0.0028868). This variant has been reported in VLCAD patient in compound heterozygous state with another likely pathogenic/pathogenic variant c.1679-6G>A (Mathur_1999, Schiff_2013). It was also detected in four alleles in one NBS study that included 693 newborns (Miller_2015); it was unspecified whether newborns with this variant were unaffected carriers or had clinical signs. Multiple clinical diagnostic laboratories have classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as likely pathogenic.

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