ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.503A>C (p.Asp168Ala) (rs745844469)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000211496 SCV000268456 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
GeneDx RCV000439614 SCV000511930 likely pathogenic not provided 2016-11-09 criteria provided, single submitter clinical testing The D168A missense variant in the ACADM gene has been reported previously in association with medium chain acyl-CoA dehydrogenase (MCAD) deficiency in an infant who was also heterozygous for the common K329E pathogenic variant, although the phase of these variants was not determined (Kennedy et al., 2010). The D168A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (S167P) has been reported in the Human Gene Mutation Database in association with MCAD deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000211496 SCV001415361 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-04-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with alanine at codon 168 of the ACADM protein (p.Asp168Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is present in population databases (rs745844469, ExAC 0.002%). This variant has been observed in an individual affected with medium chain acyl-CoA dehydrogenase deficiency (PMID: 21083904). ClinVar contains an entry for this variant (Variation ID: 226072). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Asp168 amino acid residue in ACADM. Other variant(s) that disrupt this residue have been observed in individuals with ACADM-related conditions (PMID: 23829193), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000211496 SCV000800476 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-05-02 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.