Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000667913 | SCV000792438 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2017-06-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002530729 | SCV003439710 | pathogenic | not provided | 2022-05-02 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 179 of the ABCC8 protein (p.Tyr179Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 18796520, 20685672, 30352420). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552617). 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. For these reasons, this variant has been classified as Pathogenic. |