ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.787G>A (p.Ala263Thr) (rs1308816724)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697346 SCV000825949 uncertain significance Galactosylceramide beta-galactosidase deficiency 2018-01-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 263 of the GALC protein (p.Ala263Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with another GALC variant in an individual affected with Krabbe disease (PMID: 9338580). However, in that individual, a pathogenic homozygous variant was also identified in GALC, which suggests that the c.787G>A may not contribute to disease. This variant is also known as c.739G>A (p.Ala247Thr) in the literature. Experimental studies have shown that this missense change significantly reduces GLAC enzyme activity (PMID: 27638593). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, RCV000697346 SCV001245440 uncertain significance Galactosylceramide beta-galactosidase deficiency no assertion criteria provided clinical testing

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