Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001064405 | SCV001229307 | pathogenic | Galactosylceramide beta-galactosidase deficiency | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 633 of the GALC protein (p.Thr633Met). This variant is present in population databases (rs766762599, gnomAD 0.0009%). This missense change has been observed in individual(s) with Krabbe disease (PMID: 11151421). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as T617M. ClinVar contains an entry for this variant (Variation ID: 858517). 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%. For these reasons, this variant has been classified as Pathogenic. |
Centre for Mendelian Genomics, |
RCV001064405 | SCV001367040 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2018-10-10 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3. |
Natera, |
RCV001064405 | SCV002091309 | likely pathogenic | Galactosylceramide beta-galactosidase deficiency | 2021-04-30 | no assertion criteria provided | clinical testing |