ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs397515423
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Total submissions: 4
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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 PGM1-congenital disorder of glycosylation 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000032991 SCV001584124 pathogenic PGM1-congenital disorder of glycosylation 2020-12-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PGM1 are known to be pathogenic (PMID: 22492991). This variant has been observed in individual(s) with PGM1-congenital disorder of glycosylation (PMID: 22492991, 24499211). ClinVar contains an entry for this variant (Variation ID: 39772). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg503*) in the PGM1 gene. It is expected to result in an absent or disrupted protein product.
GeneDx RCV004719669 SCV005325045 pathogenic not provided 2024-02-21 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36007526, 24499211, 22492991, 29858906)
OMIM RCV000032991 SCV000056770 pathogenic PGM1-congenital disorder of glycosylation 2012-10-01 no assertion criteria provided literature only

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