Submissions for variant NM_000017.4(ACADS):c.988C>T (p.Arg330Cys)

gnomAD frequency: 0.00046  dbSNP: rs140853839

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185690	SCV000238611	likely pathogenic	not provided	2024-07-15	criteria provided, single submitter	clinical testing	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: 26055667, 16926354, 18676165, 31813752, 32793418, 22241096, 38137468, 32778825, 19952864, 23798014, 38784038)
Fulgent Genetics, Fulgent Genetics	RCV000762888	SCV000893277	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2021-09-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000762888	SCV000942230	pathogenic	Deficiency of butyryl-CoA dehydrogenase	2024-01-04	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 330 of the ACADS protein (p.Arg330Cys). This variant is present in population databases (rs140853839, gnomAD 0.2%). This missense change has been observed in individual(s) with short-chain acyl-coA dehydrogenase (SCAD) deficiency (PMID: 16926354, 18676165; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 203557). 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) has been performed at Invitae 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 ACADS protein function. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000762888	SCV002023979	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2020-10-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000762888	SCV002033280	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2021-11-07	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252029	SCV002522862	likely pathogenic	See cases	2021-10-15	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4, PM2, PM3, PP3
Ambry Genetics	RCV004020248	SCV004916813	likely pathogenic	Inborn genetic diseases	2021-07-08	criteria provided, single submitter	clinical testing	The c.988C>T (p.R330C) alteration is located in exon 8 (coding exon 8) of the ACADS gene. This alteration results from a C to T substitution at nucleotide position 988, causing the arginine (R) at amino acid position 330 to be replaced by a cysteine (C). Based on data from the Genome Aggregation Database (gnomAD), the ACADS c.988C>T alteration was observed in 0.02% (46/282298) of total alleles studied, with a frequency of 0.15% (38/24888) in the African subpopulation. This variant has been reported in several individuals with short-chain acyl-CoA dehydrogenase deficiency (SCADD) in conjunction with a second ACADS variant (van Maldegem, 2006; Waisbren, 2008; van Maldegem, 2010; Pena, 2012; Waisbren, 2013; Maguolo, 2020). The p.R330C alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
Counsyl	RCV000762888	SCV001132320	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2016-12-21	no assertion criteria provided	clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital	RCV000762888	SCV004800871	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase		no assertion criteria provided	clinical testing	PM2_P+PM3_S+PM5+PP3+PP4