ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4147G>A (p.Gly1383Arg)

gnomAD frequency: 0.00001  dbSNP: rs748233295
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001822847 SCV002072121 likely pathogenic not provided 2017-07-16 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003321873 SCV004026511 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2023-08-16 criteria provided, single submitter curation The p.Gly1383Arg variant in ABCC8 has been reported in 2 individuals with hyperinsulinemic hypoglycemia (PMID: 20685672, 23275527), and has been identified in 0.008 (1/13146) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs748233295). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 1338249) and has been interpreted as likely pathogenic by Genetic Services Laboratory (University of Chicago). Of the 2 affected individuals, 1 was a compound heterozygote that carried a reported pathogenic variant in unknown phase, which increases the likelihood that the p.Gly1383Arg variant is pathogenic (Variation ID: 370163; PMID: 23275527). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Two additional likely pathogenic variants, resulting in a different amino acid change at the same position, (p.Gly1383Ala and p.Gly1383Glu), have been reported in association with disease in ClinVar, supporting that a change at this position may not be tolerated (Variation ID: 2137010). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive hyperinsulinemic hypoglycemia. ACMG/AMP Criteria applied: PP3, PM2, PM3_supporting, PM5 (Richards 2015).

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.