ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.600-18G>A (rs370523609)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000211531 SCV000268471 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224275 SCV000280805 pathogenic not provided 2015-03-31 criteria provided, single submitter clinical testing
Invitae RCV000211531 SCV000754920 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-12-31 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the ACADM gene. It does not directly change the encoded amino acid sequence of the ACADM protein. This variant is present in population databases (rs370523609, ExAC 0.04%). This variant has been reported in combination with a ACADM pathogenic variant in individuals with mild medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency on biochemical testing (PMID: 20434380, 26223887). However, it is uncertain if this variant can cause clinical symptoms (PMID: 20434380, 26223887). It has also been detected as heterozygous in several individuals with this condition, but the second allele was not reported (PMID: 27308838, 27477829). ClinVar contains an entry for this variant (Variation ID: 226084). Experimental studies have shown that this missense change has a weak effect on mRNA splicing (PMID: 26223887). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000211531 SCV000893475 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000224275 SCV001133288 likely pathogenic not provided 2019-02-08 criteria provided, single submitter clinical testing The best available variant frequency is uninformative. Found in at least one symptomatic patient. The gain of a new splice site is predicted. Nucleotide conservation is uninformative. Occurs in three or more cases with a recessive pathogenic variant in the same gene. Assessment of experimental evidence suggests this variant results in abnormal protein function.
Myriad Women's Health, Inc. RCV000211531 SCV001194138 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-12-20 criteria provided, single submitter clinical testing NM_000016.4(ACADM):c.600-18G>A is classified as likely pathogenic in the context of medium chain acyl-CoA dehydrogenase deficiency and is associated with a variable presentation, ranging from clinically asymptomatic to mild. Sources cited for classification include the following: PMID 31012112, 25255367, 20434380, 27477829, 26223887, 27308838 and 30626930. Classification of NM_000016.4(ACADM):c.600-18G>A is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000211531 SCV001365621 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-03-31 criteria provided, single submitter clinical testing The c.612-18G>A (also known as c.600-18G>A, NM_000016.4) variant in ACADM has been reported in at least 8 individuals affected with mild medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the compound heterozygous state (variant in trans in at least 3 of these cases was the common c.985A > G (p.K329E); Smith 2010, Grunert 2015, Narravula 2017) . Additionally, the c.612-18G>A variant segregated with disease in 1 affected family member (Grunert 2015). This variant has also been reported in ClinVar (variation ID 226084). It has been identified in 0.2% (24/10364) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). In vivo and in vitro functional assays provide evidence that this variant lead to partial missplicing of the ACADM pre-mRNA and thereby affected protein function (Grunert 2015). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. ACMG/AMP Criteria applied: PM3_strong, PS3_Moderate.

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