ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.526G>T (p.Ala176Ser) (rs200754053)

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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 RCV000211435 SCV000268486 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000211435 SCV001253680 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV000211435 SCV001417855 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-10-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 176 of the ACADM protein (p.Ala176Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs200754053, ExAC 0.02%). This variant has been observed in combination with another ACADM variant in an individual with clinical features of MCAD (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 226093). 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. 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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