Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000503846 | SCV000592999 | pathogenic | Hyperinsulinemic hypoglycemia, familial, 1 | 2017-03-17 | criteria provided, single submitter | clinical testing | |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV001280724 | SCV001468038 | likely pathogenic | not provided | 2020-08-31 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV002329189 | SCV002060220 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_000352.3(ABCC8):c.4376T>G(L1459R) is a missense variant classified as a variant of uncertain significance in the context of familial hyperinsulinism, ABCC8-related. L1459R has been observed in cases with relevant disease (PMID: 23275527). Functional assessments of this variant are not available in the literature. L1459R has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000352.3(ABCC8):c.4376T>G(L1459R) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Invitae | RCV001280724 | SCV003032969 | likely pathogenic | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1459 of the ABCC8 protein (p.Leu1459Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive diffuse hyperinsulinism (PMID: 23275527). This variant is also known as c.4379T>G (p.Leu1460Arg). ClinVar contains an entry for this variant (Variation ID: 434058). 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. 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. |