Submissions for variant NM_000017.4(ACADS):c.1130C>T (p.Pro377Leu)

gnomAD frequency: 0.00001  dbSNP: rs183161718

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000489608	SCV000577775	uncertain significance	not provided	2020-06-24	criteria provided, single submitter	clinical testing	Reported with pathogenic variants in individuals with positive newborn screening results for SCAD, but no details about confirmatory biochemical test results were provided (Wang et al., 2019); Reported with the common G209S variant in a teenager with a developmental disorder, sterotypies, dysmorphic features and mildly elevated ethylmalonic acid (Rodolfo et al., 2016); 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: 27938594, 27051597, 31620161, 27466294, 31737040, 32710939)
Invitae	RCV000635337	SCV000756737	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2022-11-25	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 ACADS protein function. ClinVar contains an entry for this variant (Variation ID: 427142). This missense change has been observed in individuals with clinical features of short chain acyl-CoA dehydrogenase deficiency (PMID: 27466294, 32710939). This variant is present in population databases (rs183161718, gnomAD 0.04%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 377 of the ACADS protein (p.Pro377Leu).
Genome-Nilou Lab	RCV000635337	SCV002033275	uncertain significance	Deficiency of butyryl-CoA dehydrogenase	2021-11-07	criteria provided, single submitter	clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital	RCV000635337	SCV004800878	pathogenic	Deficiency of butyryl-CoA dehydrogenase		no assertion criteria provided	clinical testing	PM2_P+PM3_VS+PP3+PP4