Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV001810548 | SCV002060132 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2021-11-09 | criteria provided, single submitter | clinical testing | NM_000352.3(ABCC8):c.1531C>G(L511V) is a missense variant classified as a variant of uncertain significance in the context of familial hyperinsulinism, ABCC8-related. L511V has not been observed in cases with relevant disease. Functional assessments of this variant are not available in the literature. L511V has been observed in population frequency databases (gnomAD: NFE <0.001%). In summary, there is insufficient evidence to classify NM_000352.3(ABCC8):c.1531C>G(L511V) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV002482342 | SCV002778867 | uncertain significance | Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 | 2021-11-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003107854 | SCV003779951 | uncertain significance | not provided | 2022-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 511 of the ABCC8 protein (p.Leu511Val). This variant is present in population databases (rs773345085, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ABCC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1334167). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |