Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000734633 | SCV000862789 | uncertain significance | not provided | 2018-08-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000734633 | SCV003451318 | pathogenic | not provided | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 693 of the ABCC2 protein (p.Gly693Arg). This variant is present in population databases (rs765570396, gnomAD 0.01%). This missense change has been observed in individuals with Dubin-Johnson syndrome (PMID: 31544333, 32183854). ClinVar contains an entry for this variant (Variation ID: 598277). 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 ABCC2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ABCC2 function (PMID: 32183854). For these reasons, this variant has been classified as Pathogenic. |