ClinVar Miner

Submissions for variant NM_002435.3(MPI):c.1253G>A (p.Arg418His) (rs863225087)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute RCV000202324 SCV000256095 pathogenic Congenital disorder of glycosylation type 1B criteria provided, single submitter research This variant was identified in a male who presented clinically normal until the age of 2 when he became ill with persistent vomiting and venous sinus thrombosis which resulted in a massive stroke. Subsequently he developed a seizure disorder and delayed development. Full metabolic work up was normal except for the presence of a Type I CDG profile. Given his history of normal development prior to the stroke, MPI-CDG was suggested. Enzyme assay concluded he had MPI-CDG. The enzyme assay was performed as previously reported from the Freeze lab, PMID: 9525984. “Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.” Genetic analysis revealed two single nucleotide variants inherited in a compound heterozygous fashion, NM_002435.2:c.1205A>G and NM_002435.2:c.1253G>A. The c.1253G>A variant has not been previously reported in ExAc, dbSNP or ESP, however it has been reported in COSMIC (Catalogue of Somatic Mutations in Cancer). In COSMIC, the mutation was seen in breast tissue with a sample size of 15 but the mutation was not confirmed to be somatic. The predicted protein change for NM_002435.2 is an Arginine to Histidine, which has been previously reported in SwissProt as a disease associated variant leading to CDG-Ib. This residue is highly conserved (humans through s. cerevisae with the exception of D. melanogaster).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.