ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.244dup (p.Trp82fs) (rs786204566)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185677 SCV000238597 pathogenic not provided 2018-08-28 criteria provided, single submitter clinical testing The c.244dupT mutation has been reported previously in a patient detected by newborn screening for medium chain acyl-CoA dehydrogenase (MCAD) deficiency and confirmed by a repeat screen (Andresen et al., 2001). The insertion causes a frameshift starting with codon Tryptophan 82, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 23 of the new reading frame, denoted p.Trp82LeufsX23. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185677 SCV000700255 pathogenic not provided 2017-03-01 criteria provided, single submitter clinical testing
Invitae RCV000169305 SCV000754917 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-11-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp82Leufs*23) in the ACADM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762524583, ExAC 0.005%). This variant has been reported in several individuals affected with medium-chain acyl-coenzyme A dehydrogenase deficiency, several of whom were homozygous for this variant (PMID: 11349232, 15171998, 15832312, 20036593, 23028790, 23095120). ClinVar contains an entry for this variant (Variation ID: 188934). Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000169305 SCV000918374 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-09-28 criteria provided, single submitter clinical testing Variant summary: The ACADM c.244dupT (p.Trp82LeufsX23) variant results in a premature termination codon, predicted to cause a truncated or absent ACADM protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 5/246114 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic ACADM variant (0.0054233). Multiple publications have cited the variant in affected compound heterozygote and homozygote patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000185677 SCV001245625 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196886 SCV001367520 pathogenic Episodic metabolic acidosis 2018-10-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP2. This variant was detected in heterozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198478 SCV001369425 pathogenic Myopathy 2019-08-13 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3. This variant was detected in heterozygous state.
Counsyl RCV000169305 SCV000220626 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-10-09 no assertion criteria provided clinical testing
Natera Inc RCV000169305 SCV001190644 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-05-20 no assertion criteria provided clinical testing

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