Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000708106 | SCV000837216 | pathogenic | Medium-chain acyl-coenzyme A dehydrogenase deficiency | 2019-08-23 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 11-12 of the ACADM gene. The 5' boundary is likely confined to intron 10. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. A similar variant has been reported to segregate with medium chain acyl-CoA dehydrogenase (MCAD) deficiency in a single family (PMID: 7633427). Two missense substitutions in this deleted region (p.Lys329Glu and p.Ile416Thr) have been determined to be pathogenic (PMID: 16763904,16737882, 15832312, 23028790, 16617240, 20434380, 23430840, 26947917). This suggests that this region is critical for ACADM protein function and that this deletion may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |