ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.2797C>T (p.Arg933Ter) (rs570388861)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169216 SCV000220475 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2014-07-02 criteria provided, single submitter literature only
Invitae RCV000201910 SCV001198264 pathogenic not provided 2020-08-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg933*) in the ABCC8 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs570388861, ExAC 0.006%). This variant has been observed in several individuals affected with autosomal recessive hyperinsulinism (PMID: 16429405, 26740944, 27188453). This variant is also known as p.Arg934* in the literature. ClinVar contains an entry for this variant (Variation ID: 188864). Loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169216 SCV001361438 pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2019-01-24 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.2797C>T (p.Arg933X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.4e-05 in 277126 control chromosomes (gnomAD). c.2797C>T has been reported in the literature in multiple homozygous and comopound heterozygote individuals affected with Congenital Hyperinsulinism (Wang_2017, Martinez_2016, Snider_2013). These data indicate that the variant is very likely to be associated with disease. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Johns Hopkins Genomics, Johns Hopkins University RCV000201910 SCV001762355 likely pathogenic not provided 2021-07-27 criteria provided, single submitter clinical testing ABCC8 c.2797C>T (rs570388861) is rare (<0.1%) in a large population dataset (gnomAD: 4/282772 total alleles; 0.0014%; no homozygotes) and has been reported in ClinVar (Variation ID: 188864). It has been reported in 2 individuals with congenital hyperinsulinism. This nonsense variant results in a premature stop codon in exon 23 of 39 likely leading to nonsense-mediated decay and lack of protein production. We consider ABCC8 c.2797C>T to be likely pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000201910 SCV000256802 pathogenic not provided 2015-10-07 no assertion criteria provided clinical testing

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.