Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003463382 | SCV004206560 | pathogenic | Type 2 diabetes mellitus | 2023-02-26 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003553964 | SCV004295396 | pathogenic | not provided | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 32 of the ABCC8 protein (p.Asn32Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital hyperinsulinism (PMID: 23275527, 28123437, 34055426). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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%. For these reasons, this variant has been classified as Pathogenic. |