ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.1448C>T (p.Pro483Leu)

gnomAD frequency: 0.00003  dbSNP: rs377656387
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634896 SCV000756264 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 483 of the ETFDH protein (p.Pro483Leu). This variant is present in population databases (rs377656387, gnomAD 0.004%). This missense change has been observed in individual(s) with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (PMID: 17412732, 17584774, 24190796; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 31602). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ETFDH protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ETFDH function (PMID: 17584774, 22611163). For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV001250164 SCV001424408 pathogenic Acyl-CoA dehydrogenase deficiency, glutaric acidemia type II criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV002054473 SCV002497295 likely pathogenic not provided 2022-03-01 criteria provided, single submitter clinical testing ETFDH: PM3:Strong, PM2, PS3:Supporting
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000634896 SCV002583715 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2022-09-22 criteria provided, single submitter clinical testing PS3 PM3 PM2 PM1 PP3
Revvity Omics, Revvity RCV000634896 SCV003821405 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2022-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000634896 SCV004194785 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-09-27 criteria provided, single submitter clinical testing
OMIM RCV000024306 SCV000045597 pathogenic Glutaric acidemia iic, late-onset 2007-08-01 no assertion criteria provided literature only
Natera, Inc. RCV001831606 SCV002084873 pathogenic Glutaric acidemia type 2C 2020-12-14 no assertion criteria provided clinical testing

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