ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.447G>T (p.Met149Ile) (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
Counsyl RCV000211526 SCV000800615 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-11-03 criteria provided, single submitter clinical testing
Invitae RCV000211526 SCV001219803 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-12-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 149 of the ACADM protein (p.Met149Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs121434277, ExAC 0.002%). This variant has been observed in individuals affected with MCAD deficiency (PMID: 1684086). ClinVar contains an entry for this variant (Variation ID: 226059). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different variant (c.447G>A) giving rise to the same protein effect observed here (p.Met149Ile) has been determined to be pathogenic (PMID:1684086, 9158144, Invitae). This suggests that this variant is also likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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