ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.131A>G (p.Gln44Arg) (rs751647383)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254953 SCV000321372 uncertain significance not provided 2016-06-10 criteria provided, single submitter clinical testing The Q44R variant in the ACADM gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q44R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q44R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Although missense variants in nearby residues (E43K, Q45R, Q49E) have been reported in the Human Gene Mutation Database in association with MCAD deficiency (Stenson et al., 2014), at least one of these reported variants (E43K) is interpreted by GeneDx to be a benign variant. Therefore, we interpret Q44R as variant of uncertain significance.
Invitae RCV000812228 SCV000952535 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-10-19 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 44 of the ACADM protein (p.Gln44Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs751647383, ExAC 0.06%). This variant has not been reported in the literature in individuals with ACADM-related disease. ClinVar contains an entry for this variant (Variation ID: 265023). 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. 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.

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