Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666688 | SCV000791024 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2017-04-19 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000666688 | SCV002516434 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000666688 | SCV004295344 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 306 of the GALC protein (p.Ala306Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Krabbe disease (PMID: 30089515). ClinVar contains an entry for this variant (Variation ID: 551587). 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 GALC protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GALC function (PMID: 27638593). 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. |