Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667823 | SCV000792328 | likely pathogenic | Hyperinsulinemic hypoglycemia, familial, 1 | 2017-06-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001202457 | SCV001373570 | pathogenic | not provided | 2023-12-23 | 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 1418 of the ABCC8 protein (p.Arg1418His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive familial hyperinsulinism (PMID: 15579781, 23275527, 25720052). This variant is also known as R1419H. ClinVar contains an entry for this variant (Variation ID: 552540). 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%. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 23798684). This variant disrupts the p.Arg1419 amino acid residue in ABCC8. Other variant(s) that disrupt this residue have been observed in individuals with ABCC8-related conditions (PMID: 24401662, 26316440), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001202457 | SCV002601237 | pathogenic | not provided | 2025-02-05 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.R1419H; This variant is associated with the following publications: (PMID: 34992182, 25781536, 23798684, 25720052, 34304300, 23275527, 23226049, 15579781, 34631896, 23345197) |
| Fulgent Genetics, |
RCV002485539 | SCV002799285 | pathogenic | Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 | 2022-02-28 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003459588 | SCV004197497 | pathogenic | Type 2 diabetes mellitus | 2024-01-26 | criteria provided, single submitter | clinical testing |