ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.1091T>C (p.Ile364Thr) (rs150710061)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000077876 SCV000109705 uncertain significance not provided 2015-10-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000265170 SCV000358943 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000265170 SCV000630275 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 364 of the ACADM protein (p.Ile364Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs150710061, ExAC 0.1%). This variant has been reported in an individual with abnormal newborn screening results suggestive of MCAD deficiency (PMID: 27308838). ClinVar contains an entry for this variant (Variation ID: 92253). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The threonine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and it has been identified in the the general population as well as in an individual with suspected MCAD deficiency. Currently the functional and genetic data are insufficient to ascertain the clinical impact of this variant. It has been classified as a Variant of Uncertain Significance.

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