ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.999_1011dup (p.Gln338Ter) (rs1225471006)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000003770 SCV000220486 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2014-07-07 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000478348 SCV000343451 pathogenic not provided 2016-06-26 criteria provided, single submitter clinical testing
GeneDx RCV000478348 SCV000568664 pathogenic not provided 2017-03-24 criteria provided, single submitter clinical testing The c.999_1011dup13 variant in the ACADM gene was previouslyreported in a MCAD-deficient fibroblast cell line from a patient with MCAD deficiency who harboredanother ACADM variant in trans (Yokota et al., 1991). The c.999_1011dup13 variant in theACADM gene results in the normal codon, Glutamine 338, being replaced by a Stop codon, denotedp.Q338X. The c.999_1011dup13 variant is predicted to cause loss of normal protein function eitherthrough protein truncation or nonsense-mediated mRNA decay. The c.999_1011dup13 variant is notobserved in the Exome Aggregation Consortium (Lek et al., 2016). In summary, we interpret thec.999_1011dup13 variant as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000003770 SCV000693964 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The ACADM c.999_1011dupTAGAATGAGTTAC is a frame-shift variant causing amino acid change p.Gln338X which leads to absent protein due to nonsense-mediated decay or premature truncation which is known disease mechanism. This variant is absent in 121372 chromosomes from ExAC. This variant has been reported in one patient with ACADM deficiency in compound heterozygous state with p.Lys333Glu (Yokota_1990; Yokota_1991). Multiple clinical laboratories/reputable databases have classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as Likely Pathogenic.
Invitae RCV000003770 SCV000943707 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-12-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln338*) in the ACADM gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with MCAD deficiency (PMID: 1684086). ClinVar contains an entry for this variant (Variation ID: 3587). Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003770 SCV000023935 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 1996-07-01 no assertion criteria provided literature only

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