Submissions for variant NM_000018.4(ACADVL):c.1894C>T (p.Arg632Cys)

gnomAD frequency: 0.00038  dbSNP: rs151254520

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000525816	SCV000654947	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2025-02-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 632 of the ACADVL protein (p.Arg632Cys). This variant is present in population databases (rs151254520, gnomAD 0.07%). This missense change has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 27209629; internal data). ClinVar contains an entry for this variant (Variation ID: 474894). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACADVL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl	RCV000525816	SCV000788720	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2017-01-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000525816	SCV001163429	likely pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2024-03-26	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000525816	SCV001365218	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.1894C>T (NP_000009.1:p.Arg632Cys) [GRCH38: NC_000017.11:g.7225023C>T] 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
CeGaT Center for Human Genetics Tuebingen	RCV001532300	SCV001747794	uncertain significance	not provided	2021-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001532300	SCV001825500	uncertain significance	not provided	2024-07-16	criteria provided, single submitter	clinical testing	Identified in an asymptomatic newborn who screened positive for VLCAD deficiency and was found to harbor a second variant in ACADVL (PMID: 27209629); Identified with a second ACADVL variant in an individual with 54% residual enzyme activity in patient lymphocytes (PMID: 35281659); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26385305, 28798025, 34426522, 28719003, 25352556, 26740555, 27377421, 29970176, 27209629, 35281659)
Mendelics	RCV002248780	SCV002516831	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000525816	SCV002548727	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2021-07-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000525816	SCV002088825	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2020-02-18	no assertion criteria provided	clinical testing