ClinVar Miner

Submissions for variant NM_004453.4(ETFDH):c.1211T>C (p.Met404Thr)

gnomAD frequency: 0.00001  dbSNP: rs779253471
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799942 SCV000939633 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 404 of the ETFDH protein (p.Met404Thr). This variant is present in population databases (rs779253471, gnomAD 0.006%). This missense change has been observed in individuals with ETFDH-related conditions (PMID: 22041377, 24522293, 25827849, 29336361). ClinVar contains an entry for this variant (Variation ID: 645788). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000799942 SCV002808759 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2022-05-13 criteria provided, single submitter clinical testing
Baylor Genetics RCV000799942 SCV004194792 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-03-23 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV000799942 SCV005415921 pathogenic Multiple acyl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing PM2_Supporting+PP3_Strong+PM3_VeryStrong+PP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000799942 SCV005422820 pathogenic Multiple acyl-CoA dehydrogenase deficiency 2024-10-17 criteria provided, single submitter clinical testing Variant summary: ETFDH c.1211T>C (p.Met404Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251270 control chromosomes. c.1211T>C has been reported in the literature in multiple individuals affected with Glutaric Aciduria, Type 2c (Wen_2022). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 34718578). ClinVar contains an entry for this variant (Variation ID: 645788). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV000799942 SCV001457088 likely pathogenic Multiple acyl-CoA dehydrogenase deficiency 2020-09-16 no assertion criteria provided clinical testing

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