ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.545G>A (p.Trp182Ter)

gnomAD frequency: 0.00002  dbSNP: rs767249944
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778725 SCV000915081 uncertain significance Multiple acyl-CoA dehydrogenase deficiency 2018-01-30 criteria provided, single submitter clinical testing The ETFDH c.545G>A (p.Trp182Ter) variant is a stop-gained variant predicted to result in a premature termination of the protein. The p.Trp182Ter variant has been reported in a compound heterozygous state with a missesne variant in one individual diagnosed with glutaric acidemia type II (Goodman et al. 2002). The individual presented at age 27 years and displayed decreased levels of ETFDH antigen in their fibroblasts. Control data are unavailable for the p.Trp182Ter variant, which is reported at a frequency of 0.000036 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence and potential impact of stop-gained variants, the p.Trp182Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for multiple acyl-CoA dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000778725 SCV001399748 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-09-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp182*) in the ETFDH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ETFDH are known to be pathogenic (PMID: 16510302, 23785301). This variant is present in population databases (rs767249944, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with ETFDH-related conditions (PMID: 12359134). ClinVar contains an entry for this variant (Variation ID: 631941). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000778725 SCV004040921 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-06-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV001830667 SCV002084851 pathogenic Glutaric acidemia type 2C 2020-08-11 no assertion criteria provided clinical testing

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