Submissions for variant NM_000016.6(ACADM):c.449_452del (p.Thr150fs)

dbSNP: rs786204642

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000169427	SCV000268448	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2015-02-20	criteria provided, single submitter	clinical testing
Invitae	RCV000169427	SCV000630287	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2024-01-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr150Argfs*4) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). This variant is present in population databases (rs757500332, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with MCAD deficiency (PMID: 15915086, 19064330, 22796001, 25503862). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189036). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Eurofins Ntd Llc (ga)	RCV000723370	SCV000700258	pathogenic	not provided	2017-03-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169427	SCV001361312	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2019-09-09	criteria provided, single submitter	clinical testing	Variant summary: ACADM c.449_452delCTGA (p.Thr150ArgfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 251336 control chromosomes (gnomAD). c.449_452delCTGA has been reported in the literature in compound heterozygous and homozygous individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (Ensenauer_2005, Purevsuren_2009). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	RCV000169427	SCV001739490	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2020-02-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000169427	SCV004212147	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2024-03-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000723370	SCV004220052	pathogenic	not provided	2022-12-22	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the ACADM mRNA and causes the premature termination of ACADM protein synthesis. The frequency of this variant in the general population, 0.00027 (5/18392 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (PMID: 15915086 (2005), 19064330 (2009), 21239873 (2011), 22796001 (2012), 25503862 (2015), 27856190 (2016), and 33841490 (2021)). Based on the available information, this variant is classified as pathogenic.
Counsyl	RCV000169427	SCV000220837	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2018-02-22	no assertion criteria provided	clinical testing
OMIM	RCV000169427	SCV001786673	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2024-04-04	no assertion criteria provided	literature only
Natera, Inc.	RCV000169427	SCV002092829	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency	2017-03-17	no assertion criteria provided	clinical testing
Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University	RCV000169427	SCV003838957	likely pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency		no assertion criteria provided	clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital	RCV000169427	SCV004800880	pathogenic	Medium-chain acyl-coenzyme A dehydrogenase deficiency		no assertion criteria provided	clinical testing	PVS1+PM2_P+PM3+PP4