ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.755T>G (p.Phe252Cys) (rs780510026)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000211533 SCV000268451 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Invitae RCV000211533 SCV000630295 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-08-05 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with cysteine at codon 252 of the ACADM protein (p.Phe252Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is present in population databases (rs780510026, ExAC 0.009%). This variant has been observed in several individuals with MCAD deficiency (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: 226067). 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. For these reasons, this variant has been classified as Pathogenic.

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