ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.1334G>T (p.Trp445Leu)

gnomAD frequency: 0.00001  dbSNP: rs763536356
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001052816 SCV001217044 uncertain significance Multiple acyl-CoA dehydrogenase deficiency 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 445 of the ETFDH protein (p.Trp445Leu). This variant is present in population databases (rs763536356, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ETFDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 848955). 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. This variant disrupts the p.Trp445 amino acid residue in ETFDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28468868; Invitae). 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.
GeneDx RCV001547531 SCV001767265 uncertain significance not provided 2021-04-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001832485 SCV002084868 uncertain significance Glutaric acidemia type 2C 2020-10-30 no assertion criteria provided clinical testing

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