Submissions for variant NM_000018.4(ACADVL):c.1600G>A (p.Glu534Lys)

gnomAD frequency: 0.00920  dbSNP: rs2230180

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000077907	SCV000109736	benign	not specified	2013-02-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000077907	SCV000238672	benign	not specified	2016-10-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000020074	SCV000602373	benign	Very long chain acyl-CoA dehydrogenase deficiency	2023-01-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000020074	SCV000654939	benign	Very long chain acyl-CoA dehydrogenase deficiency	2024-02-01	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000020074	SCV000803496	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Very long chain acyl-coa dehydrogenase deficiency, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.
Mendelics	RCV000020074	SCV001140232	benign	Very long chain acyl-CoA dehydrogenase deficiency	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000020074	SCV001281708	benign	Very long chain 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000077907	SCV001362324	benign	not specified	2019-11-05	criteria provided, single submitter	clinical testing	Variant summary: ACADVL c.1600G>A (p.Glu534Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0028 in 281394 control chromosomes, predominantly at a frequency of 0.029 within the African or African-American subpopulation in the gnomAD database, including 15 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10 fold of the estimated maximal expected allele frequency for a pathogenic variant in ACADVL causing Very Long Chain Acyl-CoA Dehydrogenase Deficiency phenotype (0.0029), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3 classifying the variant as benign/likely benign, while 1 reporting it as a VUS). Based on the evidence outlined above, the variant was classified as benign.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000020074	SCV001365184	benign	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.1600G>A (NP_000009.1:p.Glu534Lys) [GRCH38: NC_000017.11:g.7224388G>A] variant in ACADVL gene is interpretated to be Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BS1, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003421925	SCV004141749	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	ACADVL: BP4, BS1, BS2
Natera, Inc.	RCV000020074	SCV001459260	benign	Very long chain acyl-CoA dehydrogenase deficiency	2020-09-16	no assertion criteria provided	clinical testing