ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.1102_1105del (p.Ala369fs) (rs387906297)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000077877 SCV000225141 pathogenic not provided 2012-11-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000003775 SCV000268472 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
GeneDx RCV000077877 SCV000589303 pathogenic not provided 2018-10-17 criteria provided, single submitter clinical testing The c.1102_1105delTTAG variant in the ACADM gene has been reported previously in patients withmedium chain acyl-CoA dehydrogenase (MCAD) deficiency (Kelly et al. 1992; Ding et al. 1992; Smithet al. 2010). The c.1102_1105delTTAG variant was not observed in approximately 6500 individualsof European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it isnot a common benign variant in these populations. The deletion causes a frameshift starting withcodon Alanine 369, changes this amino acid to a Leucine residue and creates a premature Stop codonat position 18 of the new reading frame, denoted p.Ala369LeufsX18. This variant is predicted to causeloss of normal protein function either through protein truncation. In summary, we interpretc.1102_1105delTTAG to be a pathogenic variant.
Invitae RCV000003775 SCV000823926 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-01-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ACADM gene (p.Ala369Leufs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt 17 amino acids and delete the last 36 amino acids of the ACADM protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with elevated hexanoylglycine, C8, and urine adipic, suberic, sebacic acids, findings that are highly specific for medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 1356169, 20434380). This variant has also been reported to segregate with medium-chain acyl-coenzyme A dehydrogenase deficiency in a single family (PMID: 1729890). This variant is also known as c.1100_1103del in the literature. ClinVar contains an entry for this variant (Variation ID: 3592). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003775 SCV000023940 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 1992-01-01 no assertion criteria provided literature only

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