ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.379C>T (p.Arg127Ter) (rs200532368)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493135 SCV000582687 pathogenic not provided 2017-05-04 criteria provided, single submitter clinical testing The R127X variant in the GALC gene has been reported previously in the heterozygous state in the presence of a second GALC variant, in an individual with infantile-onset Krabbe disease (Tappino et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R127X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R127X as a pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590611 SCV000695677 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-04-28 criteria provided, single submitter clinical testing Variant summary: The c.379C>T (p.Arg127*) variant in GALC gene is a nonsense mutation. The mutation is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The variant has been reported in several affected individuals presented with infantile form of Krabbe via published reports. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.0032% exclusively in individuals of European descent (0.06%). This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in GALC gene (0.22%). Taken together, the variant was classified as Pathogenic.
Invitae RCV000590611 SCV000827315 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg127*) in the GALC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs200532368, ExAC 0.006%). This variant has been observed in several individuals affected with autosomal recessive Krabbe disease (PMID: 20886637, 27638593, 21824559). This variant is also known as p.R111X in the literature. ClinVar contains an entry for this variant (Variation ID: 429982). Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000590611 SCV001528218 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-01-18 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in patients with Krabbe disease [PMID 20886637]

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