Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669163 | SCV000793883 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2017-09-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002531219 | SCV003439584 | likely pathogenic | not provided | 2024-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 306 of the ABCC8 protein (p.Arg306His). This variant is not present in population databases (gnomAD no frequency). This variant has not been observed in the literature in individuals with autosomal recessive ABCC8-related conditions. This variant has been reported in individual(s) with autosomal dominant neonatal diabetes (PMID: 17919176, 29675256); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 553663). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg306 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32928245, 34304300). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |