ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1586C>T (p.Thr529Met) (rs200960659)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000410159 SCV000695669 pathogenic Galactosylceramide beta-galactosidase deficiency 2016-01-18 criteria provided, single submitter clinical testing
Invitae RCV000410159 SCV000820064 pathogenic Galactosylceramide beta-galactosidase deficiency 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 529 of the GALC protein (p.Thr529Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs200960659, ExAC 0.01%). This variant has been reported as homozygous or in combination with other GALC variants in individuals affected with Krabbe disease (PMID: 9338580, 20886637, 21824559, 23197103), and has been observed to segregate with disease in a family (PMID: 20135576, 23128445). This variant is also known as c.1538C>T (p.T513M) in the literature. ClinVar contains an entry for this variant (Variation ID: 370073). Experimental studies have shown that this missense change alters GALC trafficking to the lysosome and causes unprocessed mutant GALC trapped in the endoplasmic reticulum (ER) in transient expression assays (PMID: 26865610, 27126738). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000410159 SCV000894038 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000410159 SCV001163747 pathogenic Galactosylceramide beta-galactosidase deficiency criteria provided, single submitter clinical testing
Myriad Women's Health, Inc. RCV000410159 SCV001193824 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2019-12-09 criteria provided, single submitter clinical testing NM_000153.3(GALC):c.1586C>T(T529M, aka T513M) is classified as likely pathogenic in the context of Krabbe disease. Sources cited for classification include the following: PMID 23197103, 21824559, 9266397, 9338580, 20886637 and 23128445. Classification of NM_000153.3(GALC):c.1586C>T(T529M, aka T513M) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001093133 SCV001249965 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000410159 SCV001429611 pathogenic Galactosylceramide beta-galactosidase deficiency 2019-12-19 criteria provided, single submitter clinical testing

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