Total submissions: 4
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, |
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. |