Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000275519 | SCV000448158 | likely pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2017-04-28 | criteria provided, single submitter | clinical testing | The ETFDH c.1531G>A (p.Asp511Asn) missense variant has been reported in three studies and found in a compound heterozygous state in a total of five individuals with multiple acyl-CoA dehydrogenase deficiency (Sugai et al. 2012; Wen et al. 2013; Zhu et al. 2014). The p.Asp511Asn variant was absent from 200 control chromosomes. It is reported at a frequency of 0.00007 in the South Asian population of the Exome Aggregation Consortium but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence, the p.Asp511Asn variant is classified as likely pathogenic for multiple acyl-CoA dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Invitae | RCV000275519 | SCV002128624 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 511 of the ETFDH protein (p.Asp511Asn). This variant is present in population databases (rs780768015, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of multiple acyl-CoA dehydrogenase deficiency (PMID: 19758981, 21907580, 23628458, 31997039, 35309592). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 194057). 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 with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000275519 | SCV003800973 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-01-30 | criteria provided, single submitter | clinical testing | Variant summary: ETFDH c.1531G>A (p.Asp511Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251428 control chromosomes. c.1531G>A has been reported in the literature in multiple individuals affected with Glutaric Aciduria, Type 2c (eg. Wen_2013, Maguolo_2020, Angelin_2017, Lupica_2022, Sugai_2011, etc). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000275519 | SCV004194813 | pathogenic | Multiple acyl-CoA dehydrogenase deficiency | 2023-07-26 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000174333 | SCV000225615 | uncertain significance | not provided | 2014-12-10 | flagged submission | clinical testing |