ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.523C>T (p.Arg175Cys)

gnomAD frequency: 0.00004  dbSNP: rs762928354
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485144 SCV000564968 likely pathogenic not provided 2024-06-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 30626930, 37845732, 35309592, 34440319)
Labcorp Genetics (formerly Invitae), Labcorp RCV002525759 SCV003484016 uncertain significance Multiple acyl-CoA dehydrogenase deficiency 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 175 of the ETFDH protein (p.Arg175Cys). This variant is present in population databases (rs762928354, gnomAD 0.01%). This missense change has been observed in individual(s) with multiple Acyl-CoA dehydrogenase deficiency (PMID: 30626930). ClinVar contains an entry for this variant (Variation ID: 418182). 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 expected to disrupt ETFDH protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Arg175 amino acid residue in ETFDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18289905, 19249206, 21347544, 29988809). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV002525759 SCV004194775 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-11-27 criteria provided, single submitter clinical testing

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