ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1591C>T (p.Arg531Cys) (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 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 531 of the GALC protein (p.Arg531Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs749893889, ExAC 0.01%). This variant has been observed in individuals affected with Krabbe disease (PMID: 9338580, 30777126, 17824908). This variant is also known as R515C in the literature. ClinVar contains an entry for this variant (Variation ID: 188997). This variant has been reported to have conflicting or insufficient data to determine the effect on GALC protein 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, 28976722, 27126738). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Clinical Genetics Karolinska University Hospital,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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