Submissions for variant NM_000017.4(ACADS):c.1192C>T (p.Gln398Ter)

gnomAD frequency: 0.00006  dbSNP: rs767774362

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424844	SCV000511940	likely pathogenic	not provided	2024-08-09	criteria provided, single submitter	clinical testing	Reported as true positive unique variant in a cohort of individuals with inborn errors of metabolism (PMID: 32778825); Nonsense variant predicted to result in protein truncation, as the last 15 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32778825)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000509385	SCV000756734	pathogenic	Deficiency of butyryl-CoA dehydrogenase	2023-07-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ACADS protein in which other variant(s) (p.Arg399Gln) have been determined to be pathogenic (PMID: 32710939; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 377423). This premature translational stop signal has been observed in individual(s) with an inborn error of metabolism and/or SCAD deficiency (PMID: 32778825; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs767774362, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Gln398*) in the ACADS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 15 amino acid(s) of the ACADS protein.
Genome-Nilou Lab	RCV000509385	SCV002033261	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2021-11-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000509385	SCV005045615	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2023-05-24	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000509385	SCV000607214	not provided	Deficiency of butyryl-CoA dehydrogenase		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Counsyl	RCV000509385	SCV000800549	uncertain significance	Deficiency of butyryl-CoA dehydrogenase	2017-06-16	flagged submission	clinical testing