ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4376T>G (p.Leu1459Arg)

gnomAD frequency: 0.00001  dbSNP: rs971604271
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
Genetic Services Laboratory, University of Chicago RCV000503846 SCV000592999 pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2017-03-17 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001280724 SCV001468038 likely pathogenic not provided 2020-08-31 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV002329189 SCV002060220 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2021-11-08 criteria provided, single submitter clinical testing NM_000352.3(ABCC8):c.4376T>G(L1459R) is a missense variant classified as a variant of uncertain significance in the context of familial hyperinsulinism, ABCC8-related. L1459R has been observed in cases with relevant disease (PMID: 23275527). Functional assessments of this variant are not available in the literature. L1459R has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000352.3(ABCC8):c.4376T>G(L1459R) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV001280724 SCV003032969 likely pathogenic not provided 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1459 of the ABCC8 protein (p.Leu1459Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive diffuse hyperinsulinism (PMID: 23275527). This variant is also known as c.4379T>G (p.Leu1460Arg). ClinVar contains an entry for this variant (Variation ID: 434058). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC8 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.