ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.169G>A (p.Gly57Ser) (rs11623)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000498062 SCV000224158 pathogenic not provided 2014-10-16 criteria provided, single submitter clinical testing
GeneDx RCV000498062 SCV000589329 pathogenic not provided 2017-06-06 criteria provided, single submitter clinical testing The G57S variant in the GALC gene has been reported previously, using alternate nomenclature G41S, in both the homozygous and heterozygous states with another GALC variant in patients with Krabbe disease (Fiumara et al., 2011; Lissens et al., 2007). The G57S variant appears to be a founder mutation in Sicily where it is associated with a late-onset (onset later than 6 months) phenotype (Fiumara et al., 2011; Lissens et al., 2007). The G57S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G57S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Cells expressing the G57S variant have undetectable GALC activity in comparison to wild type (Lissens et al., 2007). We interpret G57S as a pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000173074 SCV000695672 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-03-10 criteria provided, single submitter clinical testing Variant summary: The GALC c.169G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Ser. 5/5 in-silico tools predict damaging outcome for this variant. This variant has been reported in at least 5 patients with late onset Krabbe disease in both homozygous and compound heterozygous state. This variant was not found in 16310 control chromosomes. In addition, one clinical laboratory classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.

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