ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1591C>T (p.Arg531Cys)

gnomAD frequency: 0.00001  dbSNP: rs749893889
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169377 SCV000220761 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2014-10-01 criteria provided, single submitter literature only
Invitae RCV000169377 SCV001234986 pathogenic Galactosylceramide beta-galactosidase deficiency 2022-09-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 531 of the GALC protein (p.Arg531Cys). This variant is present in population databases (rs749893889, gnomAD 0.02%). This missense change has been observed in individual(s) with Krabbe disease (PMID: 9338580, 17824908, 30777126). This variant is also known as R515C. ClinVar contains an entry for this variant (Variation ID: 188997). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GALC function (PMID: 27638593). This variant disrupts the p.Arg531 amino acid residue in GALC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10234611, 16607461, 26795590, 27126738, 28976722). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269916 SCV001450274 pathogenic not provided 2015-01-07 criteria provided, single submitter clinical testing
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV000169377 SCV001554469 pathogenic Galactosylceramide beta-galactosidase deficiency 2021-03-31 criteria provided, single submitter clinical testing

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