ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4612C>T (p.Arg1538Ter)

dbSNP: rs1411638309
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672393 SCV000797492 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2018-01-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001379884 SCV001577769 pathogenic not provided 2024-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1538*) in the ABCC8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the ABCC8 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ABCC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 556392). This variant disrupts a region of the ABCC8 protein in which other variant(s) (p.Leu1543Pro) have been determined to be pathogenic (PMID: 11867634, 15562009, 23275527). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001379884 SCV003924894 likely pathogenic not provided 2022-11-11 criteria provided, single submitter clinical testing Identified as heterozygous in a patient with hyperinsulinism in published literature (De Franco et al., 2020); Nonsense variant predicted to result in protein truncation, as the last 44 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32027066)
Fulgent Genetics, Fulgent Genetics RCV005046897 SCV005676648 likely pathogenic Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 2024-04-26 criteria provided, single submitter 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.