ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.250G>A (p.Val84Ile)

gnomAD frequency: 0.00001  dbSNP: rs775776658
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 RCV000670385 SCV000795230 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2017-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317330 SCV002500255 uncertain significance not specified 2023-06-12 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.250G>A (p.Val84Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251430 control chromosomes. c.250G>A has been reported in the literature in multiple individuals from a single three generation family affected with Monogenic Diabetes presenting as familial mild hyperglycemia (example, Gonsorcikova_2011) and continues to be cited by others (example, Li_2022, Aarthy_2021, Koufakis_2019, Tatsi_2020, Piptapolkai_2020). To our knowledge, no reports of its presence in individuals affected with Congenital Hyperinsulinism/Familial Hyperinsulinism and no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32763092, 21214702, 31110826, 34631896, 32376986, 31604004). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as a variant of uncertain significance (VUS) for Autosomal Recessive Familial Hyperinsulism and a VUS-possibly pathogenic for Monogenic Diabetes.
New York Genome Center RCV000670385 SCV002764324 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2021-08-06 criteria provided, single submitter clinical testing
Invitae RCV002531249 SCV003233990 uncertain significance not provided 2022-08-20 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 84 of the ABCC8 protein (p.Val84Ile). This variant is present in population databases (rs775776658, gnomAD 0.01%). This missense change has been observed in individual(s) with familial mild hyperglycemia (PMID: 21214702). ClinVar contains an entry for this variant (Variation ID: 554707). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.