ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.750A>G (p.Ile250Met)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001361588 SCV001557566 uncertain significance Galactosylceramide beta-galactosidase deficiency 2020-07-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 250 of the GALC protein (p.Ile250Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GALC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Ile250 amino acid residue in GALC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20410102, 8940268, 27442402, 27638593). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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.