ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.121C>T (p.Arg41Ter)

gnomAD frequency: 0.00001  dbSNP: rs773668457
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000699705 SCV000828428 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg41*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with glutaric acidemia type II (PMID: 12359134, 24190796). ClinVar contains an entry for this variant (Variation ID: 577047). 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.
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814220 SCV001755363 pathogenic Abnormality of metabolism/homeostasis 2021-07-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000699705 SCV004100083 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-09-22 criteria provided, single submitter clinical testing Variant summary: ETFDH c.121C>T (p.Arg41X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251316 control chromosomes. c.121C>T has been reported in the literature in individuals affected with Glutaric Aciduria (e.g. Goodman_2002). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 12359134). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000699705 SCV001452017 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2020-09-16 no assertion criteria provided clinical testing

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