ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1898C>T (p.Thr633Met)

gnomAD frequency: 0.00001  dbSNP: rs766762599
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
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, University Medical Centre Ljubljana 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, Inc. RCV001064405 SCV002091309 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2021-04-30 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.