ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1186C>T (p.Arg396Trp) (rs770485731)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539298 SCV000627123 pathogenic Galactosylceramide beta-galactosidase deficiency 2018-01-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 396 of the GALC protein (p.Arg396Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs770485731, ExAC 0.002%). This variant has been reported in individuals affected with Krabbe Disease (PMID: 3362311, 9338580, 26795590, 27638592, Invitae). This variant is also known as R380W in the literature. Experimental studies have shown that this missense change affects a residue involved in the binding of the GALC substrate and reduces its enzymatic activity in vitro (PMID: 21876145, 24297913, 27638593). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266086 SCV001444258 pathogenic Inborn genetic diseases 2019-10-18 criteria provided, single submitter clinical testing
GeneDx RCV001547432 SCV001767137 pathogenic not provided 2020-09-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with reduced GALC activity (Saaverda-Matiz et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as R380W using alternative nomenclature; This variant is associated with the following publications: (PMID: 9338580, 31240153, 21824559, 27638592, 26795590, 31707742, 32186243, 24297913, 21876145, 27126738, 27638593, 3362311, 23319190, 20886637)
Counsyl RCV000539298 SCV000791388 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2017-05-09 no assertion criteria provided clinical testing

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