Submissions for variant NM_014384.3(ACAD8):c.616C>T (p.Arg206Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002976019	SCV003287938	pathogenic	Deficiency of isobutyryl-CoA dehydrogenase	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg206*) in the ACAD8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACAD8 are known to be pathogenic (PMID: 16857760). This variant is present in population databases (rs369445365, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ACAD8-related conditions. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002944216	SCV003636003	pathogenic	Inborn genetic diseases	2022-09-19	criteria provided, single submitter	clinical testing	The c.616C>T (p.R206*) alteration, located in exon 6 (coding exon 6) of the ACAD8 gene, consists of a C to T substitution at nucleotide position 616. This changes the amino acid from a arginine (R) to a stop codon at amino acid position 206. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (1/251492) total alleles studied. The highest observed frequency was <0.01% (1/113768) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic.