ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.250C>T (p.Leu84Phe) (rs762114560)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000211459 SCV000268492 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
GeneDx RCV000432899 SCV000511929 pathogenic not provided 2017-10-12 criteria provided, single submitter clinical testing The L84F variant has been reported previously in trans with K329E in an individual with a severe medium chain acyl-CoA dehydrogenase (MCAD) deficiency phenotype (Smith et al., 2010). This variant has also been observed in two individuals with positive newborn screening and biochemical testing suggestive of MCAD deficiency who were also heterozygous for another variant in ACADM (Waddell et al., 2006; Touw et al. 2012). The L84F 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. The L84F variant occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret L84F to be a pathogenic variant.
Counsyl RCV000211459 SCV000677999 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2014-02-13 criteria provided, single submitter clinical testing
Invitae RCV000211459 SCV000834725 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-09-25 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 84 of the ACADM protein (p.Leu84Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs762114560, ExAC 0.009%). This variant has been observed in combination with other ACADM variants in several individuals affected with MCAD deficiency, including at least one individual with biochemical findings that are highly specific for the condition (PMID: 16291504, 21083904, 20434380). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C1). For these reasons, this variant has been classified as Pathogenic. 5

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