ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.1601C>T (p.Pro534Leu)

gnomAD frequency: 0.00001  dbSNP: rs200920510
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483304 SCV000564970 pathogenic not provided 2021-12-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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: 29581464, 30099045, 21088898, 22664151, 22995991, 27270537, 26830983, 27591119, 18289905, 30617651, 31418342, 31904027, 31589614)
Invitae RCV000818859 SCV000959493 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-08-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ETFDH protein function. ClinVar contains an entry for this variant (Variation ID: 418184). This missense change has been observed in individual(s) with glutaric acidemia type 2 (PMID: 18289905, 21088898, 22664151). 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. This variant is present in population databases (rs200920510, gnomAD 0.004%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 534 of the ETFDH protein (p.Pro534Leu).
Fulgent Genetics, Fulgent Genetics RCV000818859 SCV002801323 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2022-01-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV000818859 SCV004194778 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-10-07 criteria provided, single submitter clinical testing

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