ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.295C>T (p.Arg99Cys)

gnomAD frequency: 0.00005  dbSNP: rs371493232
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987486 SCV001136786 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000987486 SCV001575387 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-12-31 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 99 of the ETFDH protein (p.Arg99Cys). This variant is present in population databases (rs371493232, gnomAD 0.01%). This missense change has been observed in individuals with multiple acyl-CoA dehydrogenase deficiency (MADD) (PMID: 23700290, 24522293, 29336361). ClinVar contains an entry for this variant (Variation ID: 802100). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ETFDH protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
DASA RCV002255101 SCV002526387 likely pathogenic Glutaric acidemia IIc 2022-06-10 criteria provided, single submitter clinical testing The c.295C>T;p.(Arg99Cys) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 802100; PMID: 23700290; 24522293; 29336361) - PS4. The variant is present at low allele frequencies population databases (rs371493232– gnomAD 0.0004601%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The p.(Arg99Cys) was detected in trans with a Pathogenic variant (PMID: 29336361) - PM3. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is Likely Pathogenic
Fulgent Genetics, Fulgent Genetics RCV000987486 SCV002794613 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2021-11-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV000987486 SCV004194763 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-03-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV001832301 SCV002084844 likely pathogenic Glutaric acidemia type 2C 2020-01-15 no assertion criteria provided clinical testing

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