Submissions for variant NM_004453.4(ETFDH):c.1049G>A (p.Arg350Gln)

gnomAD frequency: 0.00074  dbSNP: rs139306043

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000879649	SCV001022695	likely benign	Multiple acyl-CoA dehydrogenase deficiency	2025-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000879649	SCV001305966	uncertain significance	Multiple acyl-CoA dehydrogenase deficiency	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001731970	SCV001983066	uncertain significance	not provided	2024-12-10	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22664151, 20138856, 34595457)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000879649	SCV002048566	uncertain significance	Multiple acyl-CoA dehydrogenase deficiency	2021-10-08	criteria provided, single submitter	clinical testing	The ETFDH c.1049G>A; p.Arg350Gln variant (rs139306043) is reported in the literature in a reportedly healthy individual (Er 2010). This variant is also reported in ClinVar (Variation ID: 708396), and is found in the African/African-American population with an allele frequency of 0.20% (50/24962 alleles) in the Genome Aggregation Database. The arginine at codon 350 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.284). While previously reported pathogenic variants in ETFDH are much more rare in the general population than this variant, due to limited information, the clinical significance of the p.Arg350Gln variant is uncertain at this time. References: Er TK et al. High resolution melting analysis facilitates mutation screening of ETFDH gene: applications in riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Clin Chim Acta. 2010 May 2;411(9-10):690-9. PMID: 20138856.
Revvity Omics, Revvity	RCV000879649	SCV003832283	uncertain significance	Multiple acyl-CoA dehydrogenase deficiency	2019-07-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000879649	SCV005664660	uncertain significance	Multiple acyl-CoA dehydrogenase deficiency	2024-02-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000879649	SCV001457028	uncertain significance	Multiple acyl-CoA dehydrogenase deficiency	2020-04-21	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003908392	SCV004726982	likely benign	ETFDH-related disorder	2022-05-19	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).