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

gnomAD frequency: 0.00046  dbSNP: rs140853839

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185690	SCV000238611	pathogenic	not provided	2017-12-08	criteria provided, single submitter	clinical testing	R330C missense mutations in the ACADS gene have been reported previously in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency (van Maldegem et al., 2006). The variant is found in ACADS panel(s).
Fulgent Genetics, Fulgent Genetics	RCV000762888	SCV000893277	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2021-09-23	criteria provided, single submitter	clinical testing
Invitae	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
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