ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.447G>T (p.Met149Ile)

gnomAD frequency: 0.00001  dbSNP: rs121434277
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000211526 SCV000268442 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-07-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000211526 SCV001219803 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-06-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met149 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1684086, 9158144; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACADM protein function. ClinVar contains an entry for this variant (Variation ID: 226059). This missense change has been observed in individuals with MCAD deficiency (PMID: 1684086, 9158144; Invitae). This variant is present in population databases (rs121434277, gnomAD 0.003%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 149 of the ACADM protein (p.Met149Ile).
Counsyl RCV000211526 SCV000800615 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-11-03 flagged submission clinical testing

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