Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001335146 | SCV001528215 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2018-08-02 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV001335146 | SCV003268551 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 587 of the GALC protein (p.Ile587Thr). This variant is present in population databases (rs368818550, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of Krabbe disease (PMID: 26795590). ClinVar contains an entry for this variant (Variation ID: 1032907). 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 not expected to disrupt GALC protein function. 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. |