ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1592G>A (p.Arg531His) (rs200378205)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000153296 SCV000226001 pathogenic not provided 2014-01-23 criteria provided, single submitter clinical testing
GeneDx RCV000153296 SCV000617677 likely pathogenic not provided 2020-12-23 criteria provided, single submitter clinical testing Functional studies found that R531H is associated with significantly reduced enzyme activity and impaired localization to the lysosome (Fu et al., 1999; Spratley et al. 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28976722, 26795590, 10234611, 28552323, 16607461, 24252386, 27126738)
Fulgent Genetics,Fulgent Genetics RCV000174662 SCV000894037 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000174662 SCV000951152 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 531 of the GALC protein (p.Arg531His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200378205, ExAC 0.07%). This variant has been observed in individual(s) with Krabbe disease (PMID: 10234611, 16607461, 26795590, 28976722). This variant is also known as p.Arg515His in the literature. ClinVar contains an entry for this variant (Variation ID: 167119). This variant has been reported to affect GALC protein function (PMID: 27126738). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000174662 SCV001163746 likely pathogenic Galactosylceramide beta-galactosidase deficiency criteria provided, single submitter clinical testing
Counsyl RCV000174662 SCV000486639 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2018-07-24 no assertion criteria provided clinical testing

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