Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670689 | SCV000795575 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2017-11-09 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002507172 | SCV002815654 | uncertain significance | Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 | 2022-01-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479196 | SCV004223424 | uncertain significance | not specified | 2023-11-07 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.3938G>A (p.Arg1313His) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250956 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3938G>A, described as R1314H, has been reported in the literature in at-least one individual affected with transient neonatal diabetes mellitus, the carrier father was however unaffected (Patch_2007). This variant was also reported in two individuals with Pulmonary arterial hypertension and paroxysmal atrial fibrillation, respectively, neither of which has shown a strong evidence for causality (Bohnen_2018, Puertas_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hyperinsulinism. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in reduced SUR1-dependent currents (about 25% of the WT control) and impaired pharmacological recovery of the Potassium channel by Diazoxide using Whole-cell voltage clamp in COS7 cells (Bohnen_2018). The following publications have been ascertained in the context of this evaluation (PMID: 30354297, 17919176, 30276209). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |