ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.524G>A (p.Arg175His)

dbSNP: rs121964955
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001216553 SCV001388356 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 175 of the ETFDH protein (p.Arg175His). This variant is present in population databases (rs121964955, gnomAD 0.006%). This missense change has been observed in individual(s) with multiple acyl-CoA dehydrogenase deficiency (PMID: 18289905, 20138856, 21347544, 23628458, 29988809). 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. ClinVar contains an entry for this variant (Variation ID: 31576). 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. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001216553 SCV002024515 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-06-12 criteria provided, single submitter clinical testing
Baylor Genetics RCV001216553 SCV004194818 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2023-07-17 criteria provided, single submitter clinical testing
GeneDx RCV004589522 SCV005078054 likely pathogenic not provided 2024-04-26 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: 18289905, 29988809, 22013910, 31589614, 34440319, 33823724, 30477628, 27270537, 20138856, 21347544, 25556768, 32778825, 37845732, 27591119, 33589341, 37268358, 36334790, 33438237, 19249206, 38187300, 23628458, 31136308, 35822092, 36713348, 19783111, 20370797, 36406819, 36787440, 36326420, 34041209, 33639866, 34718578)
OMIM RCV000024282 SCV000045573 pathogenic Glutaric acidemia IIc 2009-03-01 no assertion criteria provided literature only
Natera, Inc. RCV001826506 SCV002084850 pathogenic Glutaric acidemia type 2C 2020-06-01 no assertion criteria provided clinical testing

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