Submissions for variant NM_000018.4(ACADVL):c.481G>A (p.Ala161Thr)

dbSNP: rs375284481

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000271784	SCV000406312	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2017-04-28	criteria provided, single submitter	clinical testing	The ACADVL c.481G>A (p.Ala161Thr) variant has been reported in one study in a compound heterozygous state with another missense variant in one individual with very long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency (Boneh et al. 2006). The variant was also identified in a heterozygous state in the unaffected father. Control data are unavailable for this variant which is reported at a frequency of 0.00017 in the total population of the Exome Aggregation Consortium. The Ala161 residue is conserved. The evidence for this variant is limited. The p.Ala161Thr variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for VLCAD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000271784	SCV001364890	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2019-11-01	criteria provided, single submitter	clinical testing	The NM_000018.3:c.481G>A (NP_000009.1:p.Ala161Thr) [GRCH38: NC_000017.11:g.7221541G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 16488171. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3
Myriad Genetics, Inc.	RCV000271784	SCV002060365	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2021-11-03	criteria provided, single submitter	clinical testing	NM_000018.3(ACADVL):c.481G>A(A161T) is a missense variant classified as a variant of uncertain significance in the context of very-long-chain acyl-CoA dehydrogenase deficiency. A161T has been observed in cases with relevant disease (PMID: 16488171, 16950999, 20480395). Functional assessments of this variant are not available in the literature. A161T has been observed in population frequency databases (gnomAD: AMR 0.02%). In summary, there is insufficient evidence to classify NM_000018.3(ACADVL):c.481G>A(A161T) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Invitae	RCV000271784	SCV002218699	pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 161 of the ACADVL protein (p.Ala161Thr). This variant is present in population databases (rs375284481, gnomAD 0.02%). This missense change has been observed in individual(s) with VLCAD deficiency (PMID: 16488171, 16950999; Invitae). This variant is also known as A121V. ClinVar contains an entry for this variant (Variation ID: 324987). 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%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000271784	SCV003822478	uncertain significance	Very long chain acyl-CoA dehydrogenase deficiency	2022-04-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000271784	SCV004214217	likely pathogenic	Very long chain acyl-CoA dehydrogenase deficiency	2023-10-16	criteria provided, single submitter	clinical testing