Submissions for variant NM_002633.3(PGM1):c.1507C>T (p.Arg503Ter) (rs397515423)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000032991	SCV000996226	pathogenic	Congenital disorder of glycosylation type 1t	2018-12-13	criteria provided, single submitter	clinical testing	This nonsense variant found in exon 10 of 11 is predicted to result in loss of normal protein function. This variant has been previously reported as a homozygous change in two patients with Pierre Robin sequence, cleft palate, tachycardia, dilated cardiomyopathy, elevated creatine kinase, and elevated liver enzymes (PMID: 22492991, 24499211) and as a compound heterozygous change in trans with c.1172G>T p.Gly391Val in one patient with hypoglycemia, cleft palate, micrognathia, delayed speech development, elevated liver enzymes, and mild enlargment of the left ventricle (PMID: 29858906). Functional characterization of fibroblasts from both patients with a homozygous change demonstrated phosphoglucomutase activity of 7-8% as compared to controls (PMID: 22492991). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0012% (3/251206) and thus is presumed to be rare. Based on the available evidence, the c.1561C>T p.Arg521Ter variant is classified as pathogenic.
OMIM	RCV000032991	SCV000056770	pathogenic	Congenital disorder of glycosylation type 1t	2012-10-01	no assertion criteria provided	literature only