Submissions for variant NC_000001.10:g.(?_24122439)_(24144093_?)del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004583960	SCV005065074	pathogenic	Deficiency of hydroxymethylglutaryl-CoA lyase	2023-04-22	criteria provided, single submitter	clinical testing	This variant is a gross deletion of the genomic region encompassing exon(s) 3-9 of the HMGCL gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the HMGCL protein in which other variant(s) (p.His233Arg) have been determined to be pathogenic (PMID: 8798725, 9784232, 14518825, 16330550). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with HMGCL-related conditions.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004583959	SCV005065109	pathogenic	UDPglucose-4-epimerase deficiency	2023-04-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with GALE-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the GALE gene has been identified. Loss-of-function variants in GALE are known to be pathogenic (PMID: 16301867). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.