Submissions for variant NM_000018.4(ACADVL):c.1820G>A (p.Cys607Tyr)

gnomAD frequency: 0.00001  dbSNP: rs200117742

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224548	SCV000280780	uncertain significance	not provided	2015-05-14	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV001200778	SCV001365216	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.1820G>A (NP_000009.1:p.Cys607Tyr) [GRCH38: NC_000017.11:g.7224877G>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PP3
Labcorp Genetics (formerly Invitae), Labcorp	RCV001200778	SCV001417240	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 607 of the ACADVL protein (p.Cys607Tyr). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 235307). 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 ACADVL protein function with a positive predictive value of 95%. This variant disrupts the p.Cys607 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32778825; Invitae; external communication). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.